WorldWideScience

Sample records for cancer vaccines

  1. Vaccine Treatment for Prostate Cancer

    Science.gov (United States)

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer Vaccine Treatment for Prostate Cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  2. Cancer Vaccines

    Science.gov (United States)

    ... Cervical Cancer Solid Tumors Selected References Pardoll D. Cancer immunology. In: Abeloff M, Armitage J, Niederhuber J, Kastan ... 178(4):1975–1979. [PubMed Abstract] Finn OJ. Cancer immunology. New England Journal of Medicine 2008;358(25): ...

  3. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  4. Dissecting Cancer Vaccines

    Institute of Scientific and Technical Information of China (English)

    Jennifer Couzin; 丁东

    2004-01-01

    @@ If there's one thing cancer vaccine developers would like to know, it's why only a handful of patients respond strongly to their inventions. Now at an immunology② meeting here, a team of scientists reported that a set of patients with metastatic melanoma③ may be revealing an answer to that mysterious question.

  5. Cancer Vaccines: A Brief Overview.

    Science.gov (United States)

    Thomas, Sunil; Prendergast, George C

    2016-01-01

    Vaccine approaches for cancer differ from traditional vaccine approaches for infectious disease in tending to focus on clearing active disease rather than preventing disease. In this review, we provide a brief overview of different types of vaccines and adjuvants that have been investigated for the purpose of controlling cancer burdens in patients, some of which are approved for clinical use or in late-stage clinical trials, such as the personalized dendritic cell vaccine sipuleucel-T (Provenge) and the recombinant viral prostate cancer vaccine PSA-TRICOM (Prostvac-VF). Vaccines against human viruses implicated in the development and progression of certain cancers, such as human papillomavirus in cervical cancer, are not considered here. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Vaccine types considered include autologous patient-derived immune cell vaccines, tumor antigen-expressing recombinant virus vaccines, peptide vaccines, DNA vaccines, and heterologous whole-cell vaccines derived from established human tumor cell lines. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. In particular, targeted ablation of these barricades with novel agents, such as the immune checkpoint drug ipilimumab (anti-CTLA-4) approved recently for clinical use, may offer significant leverage to vaccinologists seeking to control and prevent malignancy.

  6. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  7. Preventing Cervical Cancer with HPV Vaccines

    Science.gov (United States)

    Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

  8. Cancer vaccine THERATOPE- Biomira.

    Science.gov (United States)

    2003-01-01

    Biomira is developing a therapeutic cancer vaccine [THERATOPE] for treatment of breast and other cancers. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. THERATOPE consists of the mucin antigen, sialyl-Tn (STn), a carbohydrate located on the surface of breast, colorectal and ovarian cancer cells, conjugated to keyhole limpet haemocyanin (KLH). Merck KGaA has acquired a worldwide licence to THERATOPE for treatment of breast cancer. Under the terms of the licence, Biomira and Merck KGaA, via its US affiliate, EMD Pharmaceuticals, will jointly market the vaccine in the US. Merck KGaA holds exclusive marketing rights for the rest of the world, except in Canada (where Biomira retains rights), Israel and the Palestine Autonomy Area. Merck KGaA is now collaborating on phase III development for breast cancer. Biomira stands to receive $US150 million in licence, milestone payments and equity investments. The development costs will be shared between the two companies in North America but Merck KGaA will be solely responsible for these costs in countries outside the US. Previously, Chiron Corporation had purchased a licence to THERATOPE in 1997; however, Chiron terminated this agreement in June 2000. Under the terms of the termination, Biomira paid Chiron $US2.25 million to compensate the company for its investment in the development of THERATOPE. In addition, Biomira will make another payment of $US3.25 million to Chiron upon FDA approval of the vaccine. No further payments or royalties will be made. In the third quarter of 2002, an independent review of interim data from the trial was conducted. This was the fifth scheduled review of the data by the Independent Data Safety Monitoring Board (DSMB), all of which produced a positive response. Following the completion of the review, the DSMB stated that the trial should continue and that it had no safety concerns regarding this trial. Although the data

  9. Realizing the promise of breast cancer vaccines

    Directory of Open Access Journals (Sweden)

    Jackson E

    2012-08-01

    Full Text Available Erica Jackson, Hatem SolimanUniversity of South Florida/Moffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: Breast cancer vaccines are being developed to stimulate adaptive antitumor immune responses in patients. These vaccines have the potential to treat breast cancer with minimal side effects and toxicity. However, many obstacles still need to be overcome to fully realize the vaccines' clinical benefit. A review of the literature was conducted to assess the use of vaccines in targeting transformed cells. Four vaccines currently under study were discussed, each summarizing the different vaccine platforms used to introduce target antigen to the patient's immune system. The advantages and disadvantages of each method were discussed, although no one method was found to be superior. Additional issues addressed included overcoming tumor-induced immunosuppression, immune evasion of transformed cells, the use of vaccines in combination therapy, and the challenges of using these vaccines in various clinical settings. Vaccines may be most effective in patients with minimal residual disease, as opposed to using them in the metastatic setting. Also, specific clinical trial design considerations for the use of vaccines in cancer patients, such as time-to-failure end points, were discussed. Understanding these various elements will be important to the translation of breast cancer vaccine therapy into routine clinical practice.Keywords: breast cancer, vaccine, immunotherapy, immune tolerance, peptide vaccine, dendritic cell vaccine

  10. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

    Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

  11. NIH Research Leads to Cervical Cancer Vaccine

    Science.gov (United States)

    ... Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For ... mystery. Most important, however, is to have a vaccine which potentially can ... focusing their research on helping to produce second-generation HPV vaccines ...

  12. Generation of more effective cancer vaccines

    Science.gov (United States)

    Fenoglio, Daniela; Traverso, Paolo; Parodi, Alessia; Kalli, Francesca; Zanetti, Maurizio; Filaci, Gilberto

    2013-01-01

    Cancer vaccines represent a promising therapeutic approach for which prime time is imminent. However, clinical efficacy must be improved in order for cancer vaccines to become a valid alternative or complement to traditional cancer treatments. Considerable efforts have been undertaken so far to better understand the fundamental requirements for clinically-effective cancer vaccines. Recent data emphasize that important requirements, among others, are (1) the use of multi-epitope immunogens, possibly deriving from different tumor antigens; (2) the selection of effective adjuvants; (3) the association of cancer vaccines with agents able to counteract the regulatory milieu present in the tumor microenvironment; and (4) the need to choose the definitive formulation and regimen of a vaccine after accurate preliminary tests comparing different antigen formulations. The first requirement deals with issues related to HLA restriction of tumor antigen presentation, as well as usefulness of tumor antigen spreading and counteraction of immune escape phenomena, linked to tumor antigen down-modulation, for an effective anti-cancer immune response. The second point underscores the necessity of optimal activation of innate immunity to achieve an efficient adaptive anti-cancer immune response. The third point focuses on the importance to inhibit subsets of regulatory cells. The last requirement stresses the concept that the regimen and formulation of the vaccine impacts profoundly on cancer vaccine efficacy. A new generation of cancer vaccines, provided with both immunological and clinical efficacy, will hopefully soon address these requirements. PMID:23978951

  13. Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine?

    Science.gov (United States)

    ... html Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine? Less testing could reduce risk of false positives ... said. Women vaccinated with earlier versions of the HPV vaccine -- which protect against the two worst cancer-causing ...

  14. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  15. Peptide Vaccine Therapy in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2012-08-01

    Full Text Available Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer.

  16. Prostate cancer vaccines in clinical trials.

    Science.gov (United States)

    Lubaroff, David M

    2012-07-01

    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  17. Therapeutic cancer vaccines and combination immunotherapies involving vaccination

    Directory of Open Access Journals (Sweden)

    Nguyen T

    2014-10-01

    Full Text Available Trang Nguyen,1 Julie Urban,1 Pawel Kalinski1–5 1Department of Surgery, 2Department of Immunology, 3Department of Microbiology and Infectious Disease, 4Department of Bioengineering, University of Pittsburgh, 5University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: Recent US Food and Drug Administration approvals of Provenge® (sipuleucel-T as the first cell-based cancer therapeutic factor and ipilimumab (Yervoy®/anticytotoxic T-lymphocyte antigen-4 as the first “checkpoint blocker” highlight recent advances in cancer immunotherapy. Positive results of the clinical trials evaluating additional checkpoint blocking agents (blockade of programmed death [PD]-1, and its ligands, PD-1 ligand 1 and 2 and of several types of cancer vaccines suggest that cancer immunotherapy may soon enter the center stage of comprehensive cancer care, supplementing surgery, radiation, and chemotherapy. This review discusses the current status of the clinical evaluation of different classes of therapeutic cancer vaccines and possible avenues for future development, focusing on enhancing the magnitude and quality of cancer-specific immunity by either the functional reprogramming of patients' endogenous dendritic cells or the use of ex vivo-manipulated dendritic cells as autologous cellular transplants. This review further discusses the available strategies aimed at promoting the entry of vaccination-induced T-cells into tumor tissues and prolonging their local antitumor activity. Finally, the recent improvements to the above three modalities for cancer immunotherapy (inducing tumor-specific T-cells, prolonging their persistence and functionality, and enhancing tumor homing of effector T-cells and rationale for their combined application in order to achieve clinically effective anticancer responses are addressed.Keywords: immunotherapy, cancer, vaccines

  18. Therapeutic Prostate Cancer Vaccines: A Review of the Latest Developments

    OpenAIRE

    Mohebtash, Mahsa; Madan, Ravi A.; Gulley, James L.; Arlen, Philip M.

    2008-01-01

    Therapeutic cancer vaccines are well-tolerated immunotherapy modalities designed to activate the immune system to kill cancer cells without a significant effect on normal cells. Better understanding of tumor immunology has led to improved strategies in vaccine development, which have resulted in improved outcomes. This review discusses different types of cancer vaccines, focusing predominantly on prostate cancer vaccines because of the high prevalence of prostate cancer and the wide variety o...

  19. Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163464.html Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA Agency recommends ... cancer, which is caused by the human papillomavirus (HPV). An FDA-approved vaccine called Gardasil 9 protects ...

  20. RNA-Based Vaccines in Cancer Immunotherapy.

    Science.gov (United States)

    McNamara, Megan A; Nair, Smita K; Holl, Eda K

    2015-01-01

    RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

  1. RNA-Based Vaccines in Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Megan A. McNamara

    2015-01-01

    Full Text Available RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s of interest. Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response. Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response. In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy.

  2. Guidance for peptide vaccines for the treatment of cancer

    OpenAIRE

    Yamaguchi, Yoshiyuki; Yamaue, Hiroki; Okusaka, Takuji; Okuno, Kiyotaka; Suzuki, Hiroyuki; Fujioka, Tomoaki; Otsu, Atsushi; Ohashi, Yasuo; Shimazawa, Rumiko; Nishio, Kazuto; Furuse, Junji; Minami, Hironobu; Tsunoda, Takuya; Hayashi, Yuzo; Nakamura, Yusuke

    2014-01-01

    Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system – ...

  3. Cancer Vaccines in Ovarian Cancer: How Can We Improve?

    Directory of Open Access Journals (Sweden)

    Silvia Martin Lluesma

    2016-05-01

    Full Text Available Epithelial ovarian cancer (EOC is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials.

  4. Current vaccination strategies for prostate cancer.

    NARCIS (Netherlands)

    Joniau, S.; Abrahamsson, P.A.; Bellmunt, J.; Figdor, C.G.; Hamdy, F.; Verhagen, P.; Vogelzang, N.J.; Wirth, M.; Poppel, H. van; Osanto, S.

    2012-01-01

    CONTEXT: The first therapeutic cancer vaccine demonstrating effectiveness in a phase 3 study was approved by the US Food and Drug Administration on 29 April 2010. The pivotal trial demonstrated overall survival (OS) benefit in patients treated with antigen-loaded leukapheresis cells compared with a

  5. Cancer vaccines: the perspective of the Cancer Immunology Branch, NCI.

    Science.gov (United States)

    Sogn, J A; Finerty, J F; Heath, A K; Shen, G L; Austin, F C

    1993-08-12

    The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones.

  6. Challenges facing the development of cancer vaccines.

    Science.gov (United States)

    Fishman, Mayer

    2014-01-01

    Just like any other effective immunization in medicine, cancer vaccines need to have antigens with particular specificity and immunostimulatory features, the immune responses to be elicited in the body, and therapeutic effect-regression or prevention of the cancer-must be meaningful and clinically observable. There are many choices for cancer antigens, such as tissue-specific proteins, cancer-specific proteins, class I- or class II-restricted peptides derived from those, or in situ and whole-cell-derived products are some examples. Another translational issue is that cancer patients are heterogeneous with respect to the extent to which the immune system is already activated with potential to impact the tumor growth or, conversely, the extent to which the immune system has been impaired through a prior and ongoing interaction with the tumor. Conventional or immunologic tests have potential to define a subset of patients with better chance or response, so that particular vaccines can be tested. Treatment of cancer patients is expensive, and trials are slow. To meet these challenges in practical terms will require not only careful scientific technical work for product development, coordination with clinicians to define patient subsets with diseases that can show responses, but also a comprehensive, practical implementation so that we can unlock the full potential of anticancer vaccines.

  7. Influenza vaccination in children being treated with chemotherapy for cancer

    NARCIS (Netherlands)

    G.M. Goossen; L.C.M. Kremer; M.D. van de Wetering

    2009-01-01

    Background Influenza infection is a potential cause of severe morbidity in children with cancer, therefore vaccination against influenza is recommended. However, there are conflicting data concerning the immune response to influenza vaccination in children with cancer and the value of vaccination re

  8. Vaccine Immunotherapy for Prostate Cancer

    Science.gov (United States)

    2010-05-01

    Unrelated Increased urinary urgency 2 Unrelated Decreased libido 1 Unrelated Increased erectile dysfunct. 2 Unrelated Hot flashes 1 Unrelated...Arm B – Androgen Deprivation Patients Patient Event Grade Vaccine Related APIIAADT-04 Difficulty sleeping 1 Unlikely Increased urinary freq. 2

  9. Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    William E. Gillanders

    2011-11-01

    Full Text Available New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines.

  10. Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lijin [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); Goedegebuure, Peter [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Mardis, Elaine R. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); The Genome Institute at Washington University School of Medicine, St. Louis, MO 63108 (United States); Ellis, Matthew J.C. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States); Zhang, Xiuli; Herndon, John M. [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); Fleming, Timothy P. [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Carreno, Beatriz M. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States); Hansen, Ted H. [The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States); Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Gillanders, William E., E-mail: gillandersw@wudosis.wustl.edu [Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States); The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2011-11-25

    New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines.

  11. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

  12. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  13. Listeria Vaccines for Pancreatic Cancer

    Science.gov (United States)

    2013-10-01

    Immunol 20, 77 (Jan, 2013). 13. S. K. Biswas, C. E. Lewis, J Leukoc Biol 88, 877 (Nov, 2010). 14. L. J. Bayne et al., Cancer Cell 21, 822 (Jun 12, 2012...EMT and dissemination precede prancreatic tumor formation. Cell. 2012; 148:349. 14. Bayne , L.J., Beatty, G.L., Jhala, N., Clark, C.E., Rhim, A.D...immunity in pancreatic cancer. Cancer Cell. 2012; 21:822. 15. Vonderheide, RH, Bajor, DL, Bayne , LJ, and G.L. Beatty. CD40 immunotherapy for pancreatic

  14. Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0423 TITLE: Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy PRINCIPAL INVESTIGATOR: Smita...SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0423 Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy 5b. GRANT NUMBER 5c...immune checkpoint blockade, local CTLA-4 modulation, prostate cancer immunotherapy , prostatic acid phosphatase (PAP), RNA-based vaccines 16

  15. Development of a Vaccine Targeting Triple-Negative Breast Cancer

    Science.gov (United States)

    2012-09-01

    patients with breast cancer ; (2) To evaluate the immunogenicity, clinical efficacy, and safety of an IGF-IR class II polyepitope vaccine in a mouse... breast cancer cells. Molecular cancer therapeutics 1, 707-717 (2002). 15. Koebel, C.M., et al. Adaptive immunity maintains occult cancer in an...trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer . Journal of clinical oncology : official journal of the American

  16. Dendritic Cell Cancer Vaccines: From the Bench to the Bedside

    Directory of Open Access Journals (Sweden)

    Tamar Katz

    2014-10-01

    Full Text Available The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both “passive” (e.g. strategies relying on the administration of specific T cells and “active” vaccines (e.g. peptide-directed or whole-cell vaccines have become attractive immunological approaches, inducing cell death by targeting tumor-associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target “immunosuppressive checkpoints” (anti-CTLA-4, PD-1, etc. is likely to improve and maintain immune response induced by vaccination.

  17. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  18. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  19. Preclinical and clinical development of DNA vaccines for prostate cancer.

    Science.gov (United States)

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic.

  20. An autoimmune-mediated strategy for prophylactic breast cancer vaccination.

    Science.gov (United States)

    Jaini, Ritika; Kesaraju, Pavani; Johnson, Justin M; Altuntas, Cengiz Z; Jane-Wit, Daniel; Tuohy, Vincent K

    2010-07-01

    Although vaccination is most effective when used to prevent disease, cancer vaccine development has focused predominantly on providing therapy against established growing tumors. The difficulty in developing prophylactic cancer vaccines is primarily due to the fact that tumor antigens are variations of self proteins and would probably mediate profound autoimmune complications if used in a preventive vaccine setting. Here we use several mouse breast cancer models to define a prototypic strategy for prophylactic cancer vaccination. We selected alpha-lactalbumin as our target vaccine autoantigen because it is a breast-specific differentiation protein expressed in high amounts in the majority of human breast carcinomas and in mammary epithelial cells only during lactation. We found that immunoreactivity against alpha-lactalbumin provides substantial protection and therapy against growth of autochthonous tumors in transgenic mouse models of breast cancer and against 4T1 transplantable breast tumors in BALB/c mice. Because alpha-lactalbumin is conditionally expressed only during lactation, vaccination-induced prophylaxis occurs without any detectable inflammation in normal nonlactating breast tissue. Thus, alpha-lactalbumin vaccination may provide safe and effective protection against the development of breast cancer for women in their post-child-bearing, premenopausal years, when lactation is readily avoidable and risk for developing breast cancer is high.

  1. The Prevention of Liver Cancer by HBV Vaccine Program

    Institute of Scientific and Technical Information of China (English)

    TAO Xiong

    2002-01-01

    Objective To recognize the HBV vaccine program for prevention of the hepatic cancer.Methods To discuss the relation between the HBV and hepatic cancer arising, and to discuss the immunology respond of the HBV vaccine (HBV surface antigen protein) in our patient group. Result Our data indicates that the predisposing of the HBV infection is required for the hepatic cancer arising and for the high expression of the AFP gene, and our data indicates that the HBV vaccine can induce highly immuno respond in about 78.8 % of the adult for achieving the HBV prevention status and the hepatic cancer prevention status.

  2. Swine flu vaccination for patients with cancers

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2011-01-01

    Full Text Available In oncology, vaccination is accepted as an important preventive measure. As a tertiary prevention protocol, several vaccines are recommended for the oncology patients. The newest vaccine in medicine is swine flu vaccine which is developed for prevention of novel H1N1 influenza virus infection. In this paper, the author will briefly discuss on swine flu vaccination for oncology patients.

  3. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Aurisicchio, Luigi, E-mail: aurisicchio@takis-it.it [Takis, via di Castel Romano 100, 00128 Rome (Italy); BIOGEM scarl, via Camporeale, 83031 Ariano Irpino (AV) (Italy); Ciliberto, Gennaro [Takis, via di Castel Romano 100, 00128 Rome (Italy); Dipartimento di Medicina Sperimentale e Clinica, Università degli studi di Catanzaro “Magna Graecia”, 88100 Catanzaro (Italy)

    2011-09-22

    Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs) as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad)-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP) is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.

  4. Emerging Cancer Vaccines: The Promise of Genetic Vectors

    Directory of Open Access Journals (Sweden)

    Gennaro Ciliberto

    2011-09-01

    Full Text Available Therapeutic vaccination against cancer is an important approach which, when combined with other therapies, can improve long-term control of cancer. In fact, the induction of adaptive immune responses against Tumor Associated Antigens (TAAs as well as innate immunity are important factors for tumor stabilization/eradication. A variety of immunization technologies have been explored in last decades and are currently under active evaluation, such as cell-based, protein, peptide and heat-shock protein-based cancer vaccines. Genetic vaccines are emerging as promising methodologies to elicit immune responses against a wide variety of antigens, including TAAs. Amongst these, Adenovirus (Ad-based vectors show excellent immunogenicity profile and have achieved immunological proof of concept in humans. In vivo electroporation of plasmid DNA (DNA-EP is also a desirable vaccine technology for cancer vaccines, as it is repeatable several times, a parameter required for the long-term maintenance of anti-tumor immunity. Recent findings show that combinations of different modalities of immunization (heterologous prime/boost are able to induce superior immune reactions as compared to single-modality vaccines. In this review, we will discuss the challenges and requirements of emerging cancer vaccines, particularly focusing on the genetic cancer vaccines currently under active development and the promise shown by Ad and DNA-EP heterologous prime-boost.

  5. The application of exosomes as a nanoscale cancer vaccine

    Directory of Open Access Journals (Sweden)

    Aaron Tan

    2010-11-01

    Full Text Available Aaron Tan1, Hugo De La Peña2, Alexander M Seifalian1,31UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK; 2Department of Pathology, University of Cambridge, Cambridge, UK; 3Royal Free Hampstead NHS Trust Hospital, London, UKAbstract: Cancer is a leading cause of death globally, and it is predicted and projected to continue rising as life expectancy increases. Although patient survival rates for some forms of cancers are high due to clinical advances in treatment protocols, the search for effective cancer vaccines remains the ultimate Rosetta Stone in oncology. Cervarix®, Gardasil®, and hepatitis B vaccines are currently employed in preventing certain forms of viral cancers. However, they are, strictly speaking, not ‘true’ cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells. On April 2010, a new prostate cancer vaccine Provenge® (sipuleucel-T was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy. Recent evidence suggests that the use of nanoscale particles like exosomes in immunotherapy could form a viable basis for the development of novel cancer vaccines, via antigen-presenting cell technology, to prime the immune system to recognize and kill cancer cells. Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development. Here, we review the current knowledge pertaining to exosome technology in immunotherapy and also seek to address the challenges and future directions associated with it, in hopes of bringing this exciting application a step closer toward an effective clinical reality.Keywords: exosomes, cancer vaccine, immunotherapy, nanomedicine 

  6. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shigeo Koido

    2009-01-01

    Full Text Available Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination.

  7. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Marc Mansour

    2011-08-01

    Full Text Available Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  8. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

    2011-08-05

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  9. Recent advances in the development of breast cancer vaccines

    Directory of Open Access Journals (Sweden)

    Milani A

    2014-10-01

    Full Text Available Andrea Milani,1 Dario Sangiolo,1 Massimo Aglietta,1,2 Giorgio Valabrega1,2 1Department of Oncology, University of Torino, Torino, Italy; 2FPO, Candiolo Cancer Institute, IRCCS, Torino, Italy Abstract: The manipulation of the immune system through the administration of a vaccine to direct an effective and long-lasting immune response against breast cancer (BC cells is an attractive strategy. Vaccines would have several theoretical advantages over standard therapies, including low toxicities, high specificity, and long-lasting efficacy due to the establishment of immunological memory. However, BC vaccines have failed to demonstrate meaningful results in clinical trials so far. This reflects the intrinsic difficulty in breaking the complex immune-escaping mechanisms developed by cancer cells. New vaccines should be able to elicit complex immunologic response involving multiple immune effectors such as cytotoxic and antibody-secreting B cells, innate immunity effectors, and memory cells. Moreover, especially in patients with large tumor burdens and metastatic disease, combining vaccines with other strategies, such as systemic BC therapies, passive immunotherapy, or immunomodulatory agents, could increase the effectiveness of each approach. Here, we review recent advances in BC vaccines, focusing on suitable targets and innovative strategies. We report results of most recent trials investigating active immunotherapy in BC and provide possible future perspectives in this field of research. Keywords: breast cancer, cancer vaccines, cancer immunology, HER2, MUC-1, hTERT

  10. Carbohydrate-based cancer vaccines: target cancer with sugar bullets.

    Science.gov (United States)

    Liu, Chang-Cheng; Ye, Xin-Shan

    2012-08-01

    With the booming development of glycobiology and glycochemistry, more and more structures of tumor-associated carbohydrate antigens (TACAs) are identified. Their broad expression and high specificity in cancer make them important targets to develop cancer vaccines or immunotherapies. However, most of the TACAs are T cell-independent antigens, they cannot elicit a powerful enough immune response to prevent or treat cancer. Immunotolerance and immunosuppression are more easily induced due to their endogenous properties and the declining immunity of the patients. This review summarizes the recent efforts to overcome these obstacles: coupling the carbohydrate antigens to proper carriers such as proteins or some small molecule carriers, and chemically modifying the structures of the TACAs to enhance the immunogenicity of TACAs and break the immunotolerance.

  11. Therapeutic vaccines and cancer: focus on DPX-0907

    Directory of Open Access Journals (Sweden)

    Karkada M

    2014-02-01

    Full Text Available Mohan Karkada,1,2 Neil L Berinstein,3 Marc Mansour1 1ImmunoVaccine Inc, 2Department of Microbiology/Immunology, Dalhousie University, Halifax, NS, Canada; 3Ontario Institute for Cancer Research, Toronto, ON, Canada Abstract: In an attempt to significantly enhance immunogenicity of peptide cancer vaccines, we developed a novel non-emulsion depot-forming vaccine platform called DepoVax™ (DPX. Human leukocyte antigen (HLA-A2 restricted peptides naturally presented by cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. In a phase I clinical study, the safety and immune-activating potential of DPX-0907 in advanced-stage breast, ovarian, and prostate cancer patients were examined, following encouraging results in HLA-A2 transgenic mice. The DPX-0907 vaccine was shown to be safe and well tolerated, with injection-site reactions being the most commonly reported adverse event. Vaccinated cancer patients exhibited a 61% immune response rate, with higher response rates in the breast and ovarian cancer patient cohorts. In keeping with the higher immune efficacy of this vaccine platform, antigen-specific responses were detected in 73% of immune responders after just one vaccination. In 83% of responders, peptide-specific T-cells were detected at two or more time points post-vaccination, with 64% of these patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T-cell memory, with the ability to secrete multiple type 1 cytokines. The novel DPX formulation promotes multifunctional effector/memory responses to peptide-based tumor-associated antigens. The data support the capacity of DPX-0907 to elicit type-1 biased immune responses, warranting further clinical development of the vaccine. In this review, we discuss the rationale for developing DPX-based therapeutic cancer vaccine(s, with a focus on DPX-0907, aimed at inducing efficient anti-tumor immunity that may

  12. Evolution of the health economics of cervical cancer vaccination

    NARCIS (Netherlands)

    Ferko, Nicole; Postma, Maarten; Gallivan, Steve; Kruzikas, Denise; Drummond, Michael

    2008-01-01

    This paper reviews the history of modelling for cervical cancer vaccination. We provide an interpretation and summary of conclusions pertaining to the usefulness of different models, the predicted epidemiological impact of vaccination and the cost-effectiveness of adolescent, catch-up and sex-specif

  13. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement.

    Science.gov (United States)

    Saslow, Debbie; Andrews, Kimberly S; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E; Fisher-Borne, Marcie; Smith, Robert A; Fontham, Elizabeth T H

    2016-09-01

    Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society.

  14. Cancer vaccines at an inflexion point: what next?

    Directory of Open Access Journals (Sweden)

    Obrocea Mihail

    2011-09-01

    Full Text Available Abstract With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their potential. These challenges and efforts are illustrated in a book just published on this subject, a non-exhaustive yet representative synopsis of the latest advances in cancer vaccine technologies in various stages of development. Major lessons resulting from clinical testing of cancer vaccines and other immune interventions, are being integrated in novel, cutting edge platform technologies that blur the distinction between passive and active immunotherapies as well as carry the promise of fundamentally changing and improving the management of patients with cancer.

  15. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.

    2008-01-01

    their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new......Harnessing of the immune system by the development of 'therapeutic' vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed...... on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate...

  16. IL-13 receptor-directed cancer vaccines and immunotherapy.

    Science.gov (United States)

    Nakashima, Hideyuki; Husain, Syed R; Puri, Raj K

    2012-04-01

    Many immunotherapy approaches including therapeutic cancer vaccines targeting specific tumor-associated antigens are at various stages of development. Although the significance of overexpression of (IL-13Rα2) in cancer is being actively investigated, we have reported that IL-13Rα2 is a novel tumor-associated antigen. The IL-13Rα2-directed cancer vaccine is one of the most promising approaches to tumor immunotherapy, because of the selective expression of IL-13Rα2 in various solid tumor types but not in normal tissues. In this article, we will summarize its present status and potential strategies to improve IL-13Rα2-directed cancer vaccines for an optimal therapy of cancer.

  17. Cancer vaccines at an inflexion point: what next?

    Science.gov (United States)

    Bot, Adrian; Obrocea, Mihail; Marincola, Francesco M

    2011-09-09

    With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their potential. These challenges and efforts are illustrated in a book just published on this subject, a non-exhaustive yet representative synopsis of the latest advances in cancer vaccine technologies in various stages of development. Major lessons resulting from clinical testing of cancer vaccines and other immune interventions, are being integrated in novel, cutting edge platform technologies that blur the distinction between passive and active immunotherapies as well as carry the promise of fundamentally changing and improving the management of patients with cancer.

  18. GENERAL AWARNANCE OF HUMAN PAPILLOMA VIRUS VACCINE AGAINST CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    SAFILA NAVEED

    2014-01-01

    Full Text Available We have conducted a survey program on the awarnance of HPV vaccine of cervical cancer in common people. Methods: For this survey we perform 2 steps. First we made a questionnaires in which we ask to female of different belongs to different education field either they are married or not. Secondly we gone in the different hospitals of Karachi and observe treatment, diagnosis, vaccination availability and frequency of cervical cancer. Results:From questionnaire we observed that only 1 % female are aware about cervical cancer and its vaccine i.e. HPV, even female belongs medical field are not aware about it. Form hospital survey we observed that frequency of cervical cancer is very less but in Shaukat Khanum hospital 90 cases reported out of 1803 cancer. The given treatment is radiology, chemotherapy and surgery.

  19. Infections and cancer: debate about using vaccines as a cancer control tool.

    Science.gov (United States)

    Mbulaiteye, Sam M; Buonaguro, Franco M

    2013-05-04

    In 2012, Infectious Agents and Cancer commissioned a thematic series collection of articles on Prevention of HPV related cancer. The articles have attracted wide interest and stimulated debate, including about the utility of vaccines in cancer control. The application of vaccines to cancer control fulfills a promise envisioned at the turn of the 20th century when remarkable experiments showed that some cancers were caused by infections. This suggested the possibility of applying infection-control strategies to cancer control. Vaccines represent the most practical cost-effective technology to prevent wide human suffering and death from many acute infectious diseases, such as small pox or polio. Hitherto applied to control of acute fatal infections, vaccines, if developed, might provide a potent way to control cancer. The articles in the HPV thematic series show success in developing and applying a vaccine against human papilloma virus (HPV). A vaccine is also available against hepatitis B virus (HBV), which causes liver cancer. These vaccines augment the tools available to control the associated cancers. Scientific endeavor continues for six other cancer-associated infections, mostly viruses. Not surprisingly, debate about the safety of vaccines targeting cancer has been triggered in the scientific community. Questions about safety have been raised for those populations where other means to control these cancers may be available. Although it is difficult to quantify risk from vaccines in individuals where other cancer control services exist, it is likely to be low. Vaccines are much safer today than before. Technological advancement in vaccine development and manufacture and improved regulatory review and efficient distribution have minimized substantially the risk for harm from vaccines. Formal and informal debate about the pros and cons of applying vaccines as a cancer control tools is ongoing in scientific journals and on the web. Infectious Agents and Cancer

  20. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  1. Vaccine-based clinical trials in ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Boezen, H. Marike; Melief, Kees J. M.; Nijman, Hans W.

    2011-01-01

    Ovarian cancer vaccines are one of the new treatment strategies under investigation in epithelial ovarian cancer. This article discusses the results of different immunization strategies, points out potential pitfalls in study designs and provides possible solutions for augmentation of clinical effic

  2. DNA vaccines, electroporation and their applications in cancer treatment.

    Science.gov (United States)

    Lee, Si-Hyeong; Danishmalik, Sayyed Nilofar; Sin, Jeong-Im

    2015-01-01

    Numerous animal studies and recent clinical studies have shown that electroporation-delivered DNA vaccines can elicit robust Ag-specific CTL responses and reduce disease severity. However, cancer antigens are generally poorly immunogenic, requiring special conditions for immune response induction. To date, many different approaches have been used to elicit Ag-specific CTL and anti-neoplastic responses to DNA vaccines against cancer. In vivo electroporation is one example, whereas others include DNA manipulation, xenogeneic antigen use, immune stimulatory molecule and immune response regulator application, DNA prime-boost immunization strategy use and different DNA delivery methods. These strategies likely increase the immunogenicity of cancer DNA vaccines, thereby contributing to cancer eradication. However, cancer cells are heterogeneous and might become CTL-resistant. Thus, understanding the CTL resistance mechanism(s) employed by cancer cells is critical to develop counter-measures for this immune escape. In this review, the use of electroporation as a DNA delivery method, the strategies used to enhance the immune responses, the cancer antigens that have been tested, and the escape mechanism(s) used by tumor cells are discussed, with a focus on the progress of clinical trials using cancer DNA vaccines.

  3. Human Papilloma Virus Vaccine: Future of Cervical Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Jannatul Fardows

    2016-09-01

    Full Text Available Cervical cancer is a deadly cancer that clutches lives of the women in most of the cases due to lack of consciousness about the disease in the developing countries. It remains a threat which is second only to breast cancer in overall disease burden for women throughout the world. Cervical cancer is almost a preventable disease by prophylactic vaccine and routine screening. Both Cervarix and Gardasil vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. It is safe and nearly 100% effective if given before onset of sexual activity. This review article is aimed to explore different aspects of this vaccine as well as to develop awareness among health professionals of different disciplines.

  4. Glycan changes: cancer metastasis and anti-cancer vaccines

    Indian Academy of Sciences (India)

    Min Li; Lujun Song; Xinyu Qin

    2010-12-01

    Complex carbohydrates, which are major components of the cell membrane, perform important functions in cell–cell and cell–extracellular matrix interactions, as well as in signal transduction. They comprise three kinds of biomolecules: glycoproteins, proteoglycans and glycosphingolipids. Recent studies have also shown that glycan changes in malignant cells take a variety of forms and mediate key pathophysiological events during the various stages of tumour progression. Glycosylation changes are universal hallmarks of malignant transformation and tumour progression in human cancer, which take place on the whole cells or some specific molecules. Accordingly, those changes make them prominent candidates for cancer biomarkers in the meantime. This review mainly focuses on the correlation between glycosylation and the metastasis potential of tumour cells from comprehensive aspects to further address the vital roles of glycans in oncogenesising. Moreover, utilizing these glycosylation changes to ward off tumour metastasis by means of anti-adhesion approach or devising anti-cancer vaccine is one of promising targets of future study.

  5. Current trends in cancer vaccines--a bioinformatics perspective.

    Science.gov (United States)

    Sankar, Shanju; Nayanar, Sangeetha K; Balasubramanian, Satheesan

    2013-01-01

    Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines.

  6. Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Md Kamal Hossain

    2016-07-01

    Full Text Available Aberrantly glycosylated mucin 1 (MUC1 is a recognized tumor-specific antigen on epithelial cell tumors. A wide variety of MUC1 glycopeptide anti-cancer vaccines have been formulated by many research groups. Some researchers have used MUC1 alone as an immunogen whereas other groups used different antigenic carrier proteins such as bovine serum albumin or keyhole limpet hemocyanin for conjugation with MUC1 glycopeptide. A variety of adjuvants have been used with MUC1 glycopeptides to improve their immunogenicity. Fully synthetic multicomponent vaccines have been synthesized by incorporating different T helper cell epitopes and Toll-like receptor agonists. Some vaccine formulations utilized liposomes or nanoparticles as vaccine delivery systems. In this review, we discuss the immunological evaluation of different conjugate or synthetic MUC1 glycopeptide vaccines in different tumor or mouse models that have been published since 2012.

  7. Paradigm shifting vaccines: prophylactic vaccines against latent varicella-zoster virus infection and against HPV-associated cancer

    OpenAIRE

    Frazer, Ian H.; Levin, Myron J.

    2011-01-01

    We compare the design, mechanism of action, and clinical efficacy of two recently licensed paradigm shifting vaccines. Zostavax is the first vaccine licensed to prevent disease in patients already infected with a pathogen, and is contrasted with Gardasil and Cervarix, the first vaccines designed and licensed specifically to prevent cancers.

  8. 76 FR 68768 - Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines; Availability

    Science.gov (United States)

    2011-11-07

    ... No. FDA-2009-D-0427] Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines... Considerations for Therapeutic Cancer Vaccines'' dated October 2011. The guidance document provides sponsors who wish to submit an Investigational New Drug application (IND) for a therapeutic cancer vaccine...

  9. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Junker, Niels; Ellebaek, Eva; Svane, Inge Marie

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....

  10. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...

  11. Cancer vaccines: harnessing the potential of anti-tumor immunity.

    Science.gov (United States)

    Suckow, Mark A

    2013-10-01

    Although the presence of cancer suggests failure of the immune system to protect against development of tumors, the possibility that immunity can be redirected and focused to generate an anti-tumor response offers great translational possibility. The key to this is identifying antigens likely to be present in any given tumor and functionally critical to tumor survival and growth. Such tumor-associated antigens (TAAs) are varied and optimally should be absent from normal tissue. Of particular interest are TAAs associated with the tumor stroma, as immunity directed against the stroma may restrict the ability of the tumor to grow and metastasize. Important to directing the immune system toward an effect anti-tumor response is the understanding of how TAAs are processed and how the tumor is able to evade immune elimination. The process of immunoediting happens in response to the selective pressure that the immune system places upon tumor cell populations and allows for emergence of tumor cells capable of escaping immune destruction. Efforts to harness the immune system for clinical application has been aided by vaccines based on purified recombinant protein or nucleic acid TAAs. For example, a vaccine for canine melanoma has been developed and approved based on immunization with DNA components of tyrosinase, a glycoprotein essential to melanin synthesis. The performance of cancer vaccines has been aided in some cases when supplemented with immunostimulatory molecules such as interleukin 2 or a novel extracellular matrix vaccine adjuvant. Vaccines with the broadest menu of antigenic targets may be those most likely to succeed against cancer. For this reason, tissue vaccines produced from harvested tumor material may offer significant benefit. With several cancer vaccines on the veterinary and human markets, efforts to understand basic tumor immunology are soon to yield great dividends.

  12. Tailoring DNA vaccines: designing strategies against HER2 positive cancers

    Directory of Open Access Journals (Sweden)

    Cristina eMarchini

    2013-05-01

    Full Text Available The crucial role of HER2 in epithelial transformation and its selective overexpression on cancer tissues makes it an ideal target for cancer immunotherapies such as passive immunotherapy with Trastuzumab. There are, however, a number of concerns regarding the use of monoclonal antibodies which include resistance, repeated treatments, considerable costs and side effects that make active immunotherapies against HER2 desirable alternative approaches. The efficacy of anti-HER2 DNA vaccination has been widely demonstrated in transgenic cancer-prone mice, which recapitulate several features of human breast cancers. Nonetheless, the rational design of a cancer vaccine able to trigger a long lasting immunity, and thus prevent tumor recurrence in patients, would require the understanding of how tolerance and immunosuppression regulate antitumor immune responses and, at the same time, the identification of the most immunogenic portions of the target protein. We herein retrace the findings that led to our most promising DNA vaccines that, by encoding human/rat chimeric forms of HER2, are able to circumvent peripheral tolerance. Preclinical data obtained with these chimeric DNA vaccines have provided the rationale for their use in an ongoing phase I clinical trial (EudraCT 2011-001104-34.

  13. Optimised electroporation mediated DNA vaccination for treatment of prostate cancer.

    LENUS (Irish Health Repository)

    Ahmad, Sarfraz

    2010-01-01

    ABSTRACT: BACKGROUND: Immunological therapies enhance the ability of the immune system to recognise and destroy cancer cells via selective killing mechanisms. DNA vaccines have potential to activate the immune system against specific antigens, with accompanying potent immunological adjuvant effects from unmethylated CpG motifs as on prokaryotic DNA. We investigated an electroporation driven plasmid DNA vaccination strategy in animal models for treatment of prostate cancer. METHODS: Plasmid expressing human PSA gene (phPSA) was delivered in vivo by intra-muscular electroporation, to induce effective anti-tumour immune responses against prostate antigen expressing tumours. Groups of male C57 BL\\/6 mice received intra-muscular injections of phPSA plasmid. For phPSA delivery, quadriceps muscle was injected with 50 mug plasmid. After 80 seconds, square-wave pulses were administered in sequence using a custom designed pulse generator and acustom-designed applicator with 2 needles placed through the skin central to the muscle. To determine an optimum treatment regimen, three different vaccination schedules were investigated. In a separate experiment, the immune potential of the phPSA vaccine was further enhanced with co- administration of synthetic CpG rich oligonucleotides. One week after last vaccination, the mice were challenged subcutaneously with TRAMPC1\\/hPSA (prostate cancer cell line stably expressing human PSA) and tumour growth was monitored. Serum from animals was examined by ELISA for anti-hPSA antibodies and for IFNgamma. Histological assessment of the tumours was also carried out. In vivo and in vitro cytotoxicity assays were performed with splenocytes from treated mice. RESULTS: The phPSA vaccine therapy significantly delayed the appearance of tumours and resulted in prolonged survival of the animals. Four-dose vaccination regimen provided optimal immunological effects. Co - administration of the synthetic CpG with phPSA increased anti-tumour responses

  14. Cancer vaccines: an update with special focus on ganglioside antigens.

    Science.gov (United States)

    Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

    2002-01-01

    Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by

  15. Immune modulation by dendritic-cell-based cancer vaccines

    Indian Academy of Sciences (India)

    CHAITANYA KUMAR; SAKSHI KOHLI; POONAMALLE PARTHASARATHY BAPSY; ASHOK KUMAR VAID; MINISH JAIN; VENKATA SATHYA SURESH ATTILI; BANDANA SHARAN

    2017-03-01

    The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells bymodulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing therecombinant human immune system components to target the pro-tumour microenvironment or by revitalizing theimmune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review,current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines arediscussed. Some of the DC-based vaccines under clinical trials for various cancer types are highlighted. Establishingtumour immunity involves a plethora of immune components and pathways; hence, combining chemotherapy,radiation therapy and various arms of immunotherapy, after analysing the benefits of individual therapeutic agents,might be beneficial to the patient.

  16. Clinical application of dendritic cells in cancer vaccination therapy

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Soot, Mette Line; Buus, Søren

    2003-01-01

    During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols...... for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...... endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory...

  17. Cancer vaccines at an inflexion point: what next?

    OpenAIRE

    Obrocea Mihail; Marincola Francesco M; Bot Adrian

    2011-01-01

    Abstract With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their po...

  18. Dendritic cell-based vaccine for pancreatic cancer in Japan

    Institute of Scientific and Technical Information of China (English)

    Masato Okamoto; Masanori Kobayashi; Yoshikazu Yonemitsu; Shigeo Koido; Sadamu Homma

    2016-01-01

    "Vaccell" is a dendritic cell(DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity(DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide(WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide(WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and-Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

  19. Cancer vaccines: looking to the future. Interview by Jenaid Rees.

    Science.gov (United States)

    Apostolopoulos, Vasso

    2013-10-01

    Interview by Jenaid Rees (Commissioning Editor) Vasso Apostolopoulos has been working in the field of cancer vaccines since 1991, and human clinical trials on her work have been conducted since 1994. Her work has been at the forefront of scientific research into the development of a vaccine for cancer and she has received over 90 awards and honours in recognition of her achievements. Some notable awards include, the Premier's Award for medical research, was named Young Australian of the Year (Victoria), recipient of the Channel 10/Herald Sun Young Achiever of the Year Award as well as being awarded the Order of Brigadier General of the Phoenix Battalion by the Greek President. In 1998 Apostolopoulos received the NHMRC CJ Martin Research Fellowship and worked at the Scripps Research Institute in California, USA, for 3.5 years and returned to the Austin Research Institute (VIC, Australia), and headed the Immunology and Vaccine Laboratory receiving the NHMRC RD Wright Fellowship. Upon her return to Australia, Apostolopoulos received the Victorian Tall Poppy Award, the Bodossaki Foundation Academic Prize, was inducted into the Victorian Honour roll of Women, was a torchbearer for the Melbourne leg of the International Athens 2004 Olympic Torch Relay, was named Woman of the Year, and is an Australia Day Ambassador. Her contribution into cancer research, vaccines and immunology has been extensive - publishing over 200 scientific papers and books, an inventor on 14 patents and collaborates with over 50 national and international Research Institutes and Universities. Her current research interests are in the development of new improved cancer vaccines and new modes of antigen delivery for immune stimulation. She is also interested in chronic diseases treatment and prevention through immunotherapy. She serves on the Editorial Board for Expert Review of Vaccines.

  20. Quadrivalent human papillomavirus recombinant vaccine: The first vaccine for cervical cancers

    Directory of Open Access Journals (Sweden)

    Sharma Rashmi

    2007-01-01

    Full Text Available Gardasil ® is the first quadrivalent human papillomavirus (HPV- types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 years old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.

  1. Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

    DEFF Research Database (Denmark)

    Obel, J; McKenzie, J; Buenconsejo-Lum, L E

    2015-01-01

    OBJECTIVE: To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccination...... guidelines and policies for HPV vaccination. CONCLUSION: Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation...

  2. Progress in the development of photodynamic-therapy-generated cancer vaccines

    Science.gov (United States)

    Korbelik, Mladen; Sun, Jinghai

    2003-07-01

    Upon giving an outline on vaccines in general, their history and priorities for future development, this paper gives a brief summary of the advances in the generation of cancer vaccines from the first attempts made over 100 years ago to those currently evaluted in clinical trials. This is followed by discussing hte intitial achievements in the investigation of cancer vaccines generated by photodynamic therapy (PDT). Recent contributions from our research to the understanding of how PDT-generated cancer vaccines work and their advantages compared to other types of cancer vaccines are discussed.

  3. Evolution of animal models in cancer vaccine development.

    Science.gov (United States)

    Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse

    2015-12-16

    Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide

  4. Response to influenza virus vaccination during chemotherapy in patients with breast cancer

    NARCIS (Netherlands)

    Meerveld-Eggink, A.; de Weerdt, O.; van der Velden, A. M. T.; Los, M.; van der Velden, A. W. G.; Stouthard, J. M. L.; Nijziel, M. R.; Westerman, M.; Beeker, A.; van Beek, R.; Rimmelzwaan, G. F.; Rijkers, G. T.; Biesma, D. H.

    2011-01-01

    Background: Patients receiving chemotherapy are at increased risk for influenza virus infection. Little is known about the preferred moment of vaccination during chemotherapy. Patients and methods: Breast cancer patients received influenza vaccination during FEC (5-fluorouracil, epirubicin and cyclo

  5. Business models and opportunities for cancer vaccine developers.

    Science.gov (United States)

    Kudrin, Alex

    2012-10-01

    Despite of growing oncology pipeline, cancer vaccines contribute only to a minor share of total oncology-attributed revenues. This is mainly because of a limited number of approved products and limited sales from products approved under compassionate or via early access entry in smaller and less developed markets. However revenue contribution from these products is extremely limited and it remains to be established whether developers are breaking even or achieving profitability with existing sales. Cancer vaccine field is well recognized for high development costs and risks, low historical rates of investment return and high probability of failures arising in ventures, partnerships and alliances. The cost of reimbursement for new oncology agents is not universally acceptable to payers limiting the potential for a global expansion, market access and reducing probability of commercial success. In addition, the innovation in cancer immunotherapy is currently focused in small and mid-size biotech companies and academic institutions struggling for investment. Existing R&D innovation models are deemed unsustainable in current "value-for-money" oriented healthcare environment. New business models should be much more open to collaborative, networked and federated styles, which could help to outreach global, markets and increase cost-efficiencies across an entire value chain. Lessons learned from some developing countries and especially from South Korea illustrate that further growth of cancer vaccine industry will depends not only on new business models but also will heavily rely on regional support and initiatives from different bodies, such as governments, payers and regulatory bodies.

  6. OBSERVATION ON VACCINATING Newcastle Disease Virus Vaccine with Inhalation and Preventing Recurrence of Nasopharyngeal cancer after Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To understand whether the Newcastle disease virus(NDV) vaccine can successfully vaccinate the rabbits and volunteers of cancer patients by inhalation and to observe the effects of NDV vaccine on nasopharyngeal carcinoma (NRC) patients after radiotherapy. Methods: The live NDV vaccine was vaccinated through nasal cavities of rabbits, NPC patients and other cancer patients who were treated by surgery or chemotherapy with larynx spray. The blood specimens of vein from the tested rabbits and volunteers of patients with cancer were collected before and after vaccination. The anti-NDV-antibody in serum was detected by conventional blood coagulation inhibiting method. The white blood cell (WBC) amount in blood samples was counted. In addition, the NPC patients after radiotherapy were divided into both test group and control group with random match. The both were followed-up by multiple kinds of way in order to understand effects of NDV immunotherapy for NPC. Results: The anti-NDV-antibody level of the rabbits and the patients with NPC rose significantly after vaccination. The WBC amount of cancer patients treated by surgery or chemotherapy also rose significantly after vaccination. The recurrence rate (3.23%) of NRC patients in test group who received immunotherapy of NDV vaccine for 4 to 10 treatment courses within 3 years after end of radiotherapy were significantly lower than that (25.81%) of the control group (P<0.025). Conclusion: The NDV vaccine La Sota strain can vaccinate the rabbits and the cancer patients in success by inhalation. And it has remarkable effect to decrease 3 year recurrence rate of NRC patients after radiotherapy.

  7. Dendritic cell targeting vaccine for HPV-associated cancer

    Science.gov (United States)

    Yin, Wenjie; Duluc, Dorothée; Joo, HyeMee; Oh, SangKon

    2017-01-01

    Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients. Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8+ T cells, from the blood of HPV16+ head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16

  8. Therapeutic vaccines in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Socola F

    2013-09-01

    Full Text Available Francisco Socola,1 Naomi Scherfenberg,2 Luis E Raez3 1Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 2University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 3Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, Florida, USA Abstract: Non-small cell lung cancer (NSCLC unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-β in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3, an antigen-based vaccine, has shown promising results in MAGE-A3+ NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin 1 protein (MUC-1, a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF vaccine that induces anti-EGF antibody production and prevents EGF

  9. TPD52: A Novel Vaccine Target for Prostate Cancer

    Science.gov (United States)

    2009-09-01

    Cancer Res 1996;2:1255–61. 51. Bright RK, Vocke CD, Emmert- Buck MR, et al. Generation and genetic characterization of immortal human prostate epithelial...total of 2 injections given at 14 day intervals followed by a booster immunization given 35 days after the second immunization. Empty vector DNA...TCCATGACGTTCCTGA CGTT) [25]. The protein vaccines were administered as an alum precipitate and a booster of the same dose was given approximately 2 weeks

  10. Interview. Cancer vaccines and immunotherapy of autoimmune diseases.

    Science.gov (United States)

    Apostolopoulos, Vasso

    2009-01-01

    Vasso Apostolopoulos heads the Immunology and Vaccine Laboratory of Burnet Institute (Australia). She completed her PhD in 1995 at the Austin Research Institute (Australia). Her work on cancer vaccine development has been in clinical trial since 1994. In the last 16 years, she has received more than 100 awards/honors for her achievements. Most notable are the Premiers Award for Medical Research, Victorian Young Australian of the Year, Channel 10/Herald Sun Young Achiever of the Year, Victorian Tall Poppy, inductee into the Victorian Honour Roll of Women, a torchbearer in the International Athens 2004 Olympic Torch Relay and was named Woman of the Year. In 1998, she received the prestigious NHMRC CJ Martin Fellowship and undertook research at the Scripps Research Institute (CA, USA) until 2001. In 2001, she returned to the Austin Research Institute (now the Burnet Institute) and was a NHMRC RD Wright Fellow until 2007. She is currently a Professor, Principle Research Fellow, Sir Zelman Cowen Cancer Research Fellow, Australia Day Ambassador and a Patron of the Womens Health Network. She has published more than 120 papers and books and is an inventor on 12 patents. She is on the board and a regular reviewer for a number of journals. Her current interests are in the development of new improved cancer vaccines and new modes of antigen delivery for immune stimulation. She is also interested in the 3D x-ray crystal structures of peptide-MHC complexes.

  11. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... synergistic effect of combining CG antigen immunotherapeutic strategies with epigenetic modifiers. WHAT THE READER WILL GAIN: The reader will gain an overview of the past, present and future role of CG antigens in cancer immunotherapy. TAKE HOME MESSAGE: Chemoimmunotherapy using epigenetic drugs and CG...

  12. Advances and perspectives of colorectal cancer stem cell vaccine.

    Science.gov (United States)

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  13. Vaccines against human papillomavirus infections: protection against cancer, genital warts or both?

    Science.gov (United States)

    Joura, E A; Pils, S

    2016-12-01

    Since 2006, three vaccines against infections and disease caused by human papillomavirus (HPV) became available in Europe-in 2006 a quadrivalent HPV 6/11/16/18 vaccine, in 2007 a bivalent HPV 16/18 vaccine and in 2015 a nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. HPV 16 and 18 are the most oncogenic HPV strains, causing about 70% of cervical and other HPV-related cancers, HPV 6 and 11 cause 85% of all genital warts. The additional types of the polyvalent vaccine account for about 20% of invasive cervical cancer and >35% of pre-cancer. The potential differences between these vaccines caused some debate. All three vaccines give a robust and long-lasting protection against the strains in the various vaccines. The promise of cross-protection against other types (i.e. HPV 31/33/45) and hence a broader cancer protection was not fulfilled because these observations were confounded by the vaccine efficacy against the vaccine types. Furthermore, cross-protection was not consistent over various studies, not durable and not consistently seen in the real world experience. The protection against disease caused by oncogenic HPV strains was not compromised by the protection against low-risk types causing genital warts. The most effective cancer protection to date can be expected by the nonavalent vaccine, data indicate a 97% efficacy against cervical and vulvovaginal pre-cancer caused by these nine HPV types.

  14. Adjuvants for peptide-based cancer vaccines

    OpenAIRE

    Khong, Hiep; Overwijk, Willem W

    2016-01-01

    Cancer therapies based on T cells have shown impressive clinical benefit. In particular, immune checkpoint blockade therapies with anti-CTLA-4 and anti-PD-1/PD-L1 are causing dramatic tumor shrinkage and prolonged patient survival in a variety of cancers. However, many patients do not benefit, possibly due to insufficient spontaneous T cell reactivity against their tumors and/or lacking immune cell infiltration to tumor site. Such tumor-specific T cell responses could be induced through anti-...

  15. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  16. Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer

    Directory of Open Access Journals (Sweden)

    L. Stewart Massad

    2015-04-01

    Conclusion: Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.

  17. Vaccine therapy with sipuleucel-T (Provenge) for prostate cancer.

    Science.gov (United States)

    Thara, Eddie; Dorff, Tanya B; Pinski, Jacek K; Quinn, David I

    2011-08-01

    As the most common malignancy among North American males, prostate cancer causes more than 30,000 deaths each year. After local and hormonal treatments, a great number of patients ultimately progressed to castrate-resistant prostate cancer (CRPC), in which chemotherapy provides a small survival advantage, but with significant toxicities. In the past decade, prostate cancer has become a target for several immunotherapeutic approaches. Sipuleucel-T (Provenge®, or APC8015) is a novel cancer vaccine developed from autologous dendritic cells (DC) loaded with engineered fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Phase I and Phase II trials show that the vaccine is safe and effective in creating immune responses toward the fusion-protein target antigen, PAP-GM-CSF also call PA2024. Recent Phase III studies also demonstrated sipuleucel-T's efficacy in prolonging median survival in patients with CRPC, despite little or no effect on clinical disease progression or surrogates such as serum PSA kinetics. Subsequently, the United States Food and Drug Administration approved sipuleucel-T for the treatment of asymptomatic or minimally symptomatic CRPC in April 2010. Filings are projected with international regulatory agencies in 2011. While the development of sipuleucel-T provides an option for patients with early CRPC, it also introduces physicians and researchers to new unanswered questions regarding its optimal clinical use and questions about mechanism of action and combination and sequencing with other agents.

  18. Human Papillomavirus Vaccine as an Anticancer Vaccine: Collaborative Efforts to Promote Human Papillomavirus Vaccine in the National Comprehensive Cancer Control Program.

    Science.gov (United States)

    Townsend, Julie S; Steele, C Brooke; Hayes, Nikki; Bhatt, Achal; Moore, Angela R

    2017-03-06

    Widespread use of the human papillomavirus (HPV) vaccine has the potential to reduce incidence from HPV-associated cancers. However, vaccine uptake among adolescents remains well below the Healthy People 2020 targets. The Centers for Disease Control and Prevention (CDC) National Comprehensive Cancer Control Program (NCCCP) awardees are well positioned to work with immunization programs to increase vaccine uptake. The CDC chronic disease management information system was queried for objectives and activities associated with HPV vaccine that were reported by NCCCP awardees from 2013 to 2016 as part of program reporting requirements. A content analysis was conducted on the query results to categorize interventions according to strategies outlined in The Guide to Community Preventive Services and the 2014 President's Cancer Panel report. Sixty-two percent of NCCCP awardees had planned or implemented at least one activity since 2013 to address low HPV vaccination coverage in their jurisdictions. Most NCCCP awardees (86%) reported community education activities, while 65% reported activities associated with provider education. Systems-based strategies such as client reminders or provider assessment and feedback were each reported by less than 25% of NCCCP awardees. Many NCCCP awardees report planning or implementing activities to address low HPV vaccination coverage, often in conjunction with state immunization programs. NCCCP awardees can play a role in increasing HPV vaccination coverage through their cancer prevention and control expertise and access to partners in the healthcare community.

  19. Intra-Prostate Cancer Vaccine Inducer

    Science.gov (United States)

    2006-07-01

    immu- nogenicity while normal antigens are tolerated during development and are of much weaker im- munogenicity. (2) Autoimmunity induction is or...RF, Barr H, et al. Palliation of patients with dysphagia due to advanced esophageal cancer by endoscopic injection of cisplatin/epinephrine injectable...SA, McCormack NA, Lavender D, Haworth R. The assessment of local tolerance , acute toxicity, and DNA biodistribution following particle-mediated

  20. Issues and challenges in implementing cervical cancer screenings in the emergence of HPV vaccination in Thailand.

    Science.gov (United States)

    Juntasopeepun, Phanida; Davidson, Patricia M; Srisomboon, Jatupol

    2012-01-01

    The discovery of the HPV vaccine has been a major breakthrough in preventing cervical cancer and other HPV-related diseases around the globe. Cervical cancer is a significant public health problem in Thailand. Despite the long-time availability of cervical cancer screening programs in Thailand, the uptake among the target female population remains low. HPV vaccines were approved by the Food and Drug Administration of Thailand in 2007. As of March 2011, due to financial limitations, HPV vaccines have still not been included in the national immunization program under the public health benefit plans although individuals has the option to pay privately for the vaccine. This paper discusses the issues and challenges in implementing cervical cancer screening programs in the era of HPV vaccination in Thailand. Recommendations to increase the uptake of cervical cancer screening and further research to inform a policy regarding the cervical cancer screening measures are proposed.

  1. Recombinant cancer vaccines and new vaccine targets. Interview by Jenaid Rees.

    Science.gov (United States)

    Schlom, Jeffrey

    2013-10-01

    Interview by Jenaid Rees, Commissioning Editor Jeffrey Schlom obtained his PhD from Rutgers University (NJ, USA). After obtaining his PhD, he worked at Columbia University (NY, USA) before moving in 1973 to the National Cancer Institute, National Institutes of Health (MD, USA). Since then he has served as the Chief of several sections, including his present position as the Chief of the Laboratory of Tumor Immunology and Biology in the Center for Cancer Research which he has held for the past 30 years. During this period, he has worked as an Adjunct Professor at George Washington University (Washington, DC, USA), served on the Editorial Board of several journals and holds membership in a number of committees. He holds over 30 patents and patent applications in the areas of vaccines, tumor antigens and monoclonal antibodies and has received honors and awards throughout his career. Jeffrey Schlom has been involved in translational research involving the immunotherapy of a range of carcinomas and predominantly works in the areas of tumor immunology, mechanisms of tumor cell-immune cell interactions and immune mechanisms. He has recently been working on the design and characterization of recombinant vaccines for cancer therapy.

  2. Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Maurizio Chiriva-Internati

    Full Text Available Sperm protein (Sp17 is an attractive target for ovarian cancer (OC vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17 was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

  3. Establishing the pig as a large animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon;

    2015-01-01

    . Previous development of therapeutic cancer vaccines has largely been based on studies in mice, and the majority of these candidate vaccines failed to induce therapeutic responses in the subsequent human clinical trials. Given that antigen dose and vaccine volume in pigs are translatable to humans...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer....

  4. Update on vaccine development for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Nina Chi

    2010-08-01

    Full Text Available Nina Chi1, Jodi K Maranchie2,3, Leonard J Appleman3,4, Walter J Storkus1,3,51Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 2Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 3University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States; 4Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 5Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAAbstract: Renal cell carcinoma (RCC remains a significant health concern that frequently presents as metastatic disease at the time of initial diagnosis. Current first-line therapeutics for the advanced-stage RCC include antiangiogenic drugs that have yielded high rates of objective clinical response; however, these tend to be transient in nature, with many patients becoming refractory to chronic treatment with these agents. Adjuvant immunotherapies remain viable candidates to sustain disease-free and overall patient survival. In particular, vaccines designed to optimize the activation, maintenance, and recruitment of specific immunity within or into the tumor site continue to evolve. Based on the integration of increasingly refined immunomonitoring systems in both translational models and clinical trials, allowing for the improved understanding of treatment mechanism(s of action, further refined (combinational vaccine protocols are currently being developed and evaluated. This review provides a brief history of RCC vaccine development, discusses the successes and limitations in such approaches, and provides a rationale for developing combinational vaccine approaches that may provide improved clinical benefits to patients with RCC.Keywords: renal cell carcinoma, vaccines, immunotherapy, combinational therapy, cellular immunity

  5. Therapeutic vaccines for cancer: an overview of clinical trials.

    Science.gov (United States)

    Melero, Ignacio; Gaudernack, Gustav; Gerritsen, Winald; Huber, Christoph; Parmiani, Giorgio; Scholl, Suzy; Thatcher, Nicholas; Wagstaff, John; Zielinski, Christoph; Faulkner, Ian; Mellstedt, Håkan

    2014-09-01

    The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

  6. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  7. Cervical cancer and HPV: Awareness and vaccine acceptability among parents in Morocco.

    Science.gov (United States)

    Mouallif, Mustapha; Bowyer, Harriet L; Festali, Soukaina; Albert, Adelin; Filali-Zegzouti, Younes; Guenin, Samuel; Delvenne, Philippe; Waller, Jo; Ennaji, Moulay Mustapha

    2014-01-01

    Cervical cancer is a major public health concern in Morocco where it represents the second most common and lethal cancer in women. Human papillomavirus (HPV) vaccines have been licensed in Morocco since 2008 but there are no available data on their acceptability. This study aimed to assess awareness of HPV and the vaccine, and to identify factors associated with acceptability of the vaccine among parents in Morocco. We carried out a questionnaire-based survey using face-to-face interviews in a sample of 852 parents (670 mothers and 182 fathers) with at least one unmarried daughter ≤26 years. We collected data within public and private health centres and clinics in four regions in Morocco between July and August 2012. The main outcome measure was parental acceptability of the HPV vaccine for their daughter(s). Responses revealed very low awareness of HPV infection (4.7%) and the HPV vaccine (14.3%). None of the participants had vaccinated their daughter(s) against HPV and vaccine acceptability was low among mothers (32%) and fathers (45%). Higher education and income, previous awareness of the HPV vaccine and endorsement of the belief that a recommendation from the Ministry of Health or a doctor to have the vaccine would be encouraging, were associated with mothers' HPV vaccine acceptability. Non-acceptability among mothers was associated with having more than two daughters, believing the vaccine was expensive, lack of information and believing that whatever happens to an individual's health is God's will. The only factor associated with the fathers' acceptability of the vaccine was the cost of the vaccine. Increasing HPV and HPV vaccine awareness through educational campaigns, along with active recommendation by physicians and a publically funded vaccination programme could increase parental acceptability of the HPV vaccine in Morocco.

  8. Freund's vaccine adjuvant promotes Her2/Neu breast cancer

    Directory of Open Access Journals (Sweden)

    Woditschka Stephan

    2009-01-01

    Full Text Available Abstract Background Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. Methods The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Results Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Conclusion Our data suggests that systemic inflammation induced by Freund's adjuvant (FA promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.

  9. Progress and challenges in the vaccine-based treatment of head and neck cancers

    Directory of Open Access Journals (Sweden)

    Venuti Aldo

    2009-05-01

    Full Text Available Abstract Head and neck (HN cancer represents one of the most challenging diseases because the mortality remains high despite advances in early diagnosis and treatment. Although vaccine-based approaches for the treatment of advanced squamous cell carcinoma of the head and neck have achieved limited clinical success, advances in cancer immunology provide a strong foundation and powerful new tools to guide current attempts to develop effective cancer vaccines. This article reviews what has to be rather what has been done in the field for the development of future vaccines in HN tumours.

  10. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    OpenAIRE

    Shigeo Koido; Eiichi Hara; Sadamu Homma; Yoshihisa Namiki; Toshifumi Ohkusa; Jianlin Gong; Hisao Tajiri

    2010-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived...

  11. The pharmaceuticalization of sexual risk: vaccine development and the new politics of cancer prevention.

    Science.gov (United States)

    Mamo, Laura; Epstein, Steven

    2014-01-01

    Vaccine development is a core component of pharmaceutical industry activity and a key site for studying pharmaceuticalization processes. In recent decades, two so-called cancer vaccines have entered the U.S. medical marketplace: a vaccine targeting hepatitis B virus (HBV) to prevent liver cancers and a vaccine targeting human papillomavirus (HPV) to prevent cervical and other cancers. These viruses are two of six sexually transmissible infectious agents (STIs) that are causally linked to the development of cancers; collectively they reference an expanding approach to apprehending cancer that focuses attention simultaneously "inward" toward biomolecular processes and "outward" toward risk behaviors, sexual practices, and lifestyles. This paper juxtaposes the cases of HBV and HPV and their vaccine trajectories to analyze how vaccines, like pharmaceuticals more generally, are emblematic of contemporary pharmaceuticalization processes. We argue that individualized risk, in this case sexual risk, is produced and treated by scientific claims of links between STIs and cancers and through pharmaceutical company and biomedical practices. Simultaneous processes of sexualization and pharmaceuticalization mark these cases. Our comparison demonstrates that these processes are not uniform, and that the production of risks, subjects, and bodies depends not only on the specificities of vaccine development but also on the broader political and cultural frames within which sexuality is understood.

  12. Dendritic cell vaccines in cancer immunotherapy: from biology to translational medicine

    Institute of Scientific and Technical Information of China (English)

    Hongmei Xu; Xuetao Cao

    2011-01-01

    According to the GLOBOCAN reports,there were about 12.7 million cancer cases and 7.6 million cancer deaths in 2008,and the cancer burden continues to increase worldwide [1].At present,the common treatments for cancer include surgery,chemotherapy,radiotherapy,and immunotherapy.Immunotherapy aims to enhance or regulate the patient's own immune response to fight against tumors.It represents a novel and effective strategy in cancer treatments,but,generally,its efficacy needs to be improved [2].Cancer vaccination is an important and promising approach in cancer immunotherapy.For many years,prophylactic vaccines have exhibited profound accomplishment in preventing serious infectious diseases in humankind,including polio,small pox,and diphtheria.However,cancer vaccines are vastly different from the prophylactic vaccines in that they are aimed to eliminate preexisting tumors.Furthermore,the immune system is immunosuppressed in most cancer patients,so it is much more difficult to develop effective cancer vaccines.

  13. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S

    2008-01-01

    Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...... on dendritic cells pulsed with an allogenic tumor cell lysate. Twenty patients with advanced colorectal cancer were consecutively enrolled. Dendritic cells (DC) were generated from autologous peripheral blood mononuclear cells and pulsed with allogenic tumor cell lysate containing high levels of cancer...

  14. FDA Approves Two HPV Vaccines: Cervarix for Girls, Gardasil for Boys | Division of Cancer Prevention

    Science.gov (United States)

    The FDA has approved a second vaccine to prevent cervical cancer and cervical precancers, the vaccine’s manufacturer, GlaxoSmithKline (GSK), announced last week. The approval is based on data from a large clinical trial showing that the vaccine, Cervarix, prevented precancerous lesions in 93 percent of those who received the full vaccine sequence of three injections over 6 months. |

  15. Translational cancer vaccine: from mouse to human to cat

    Science.gov (United States)

    Levenson, Richard

    2015-03-01

    Acanthomatous ameloblastoma is a locally invasive tumor arising in the gingiva that can progress rapidly, invade and destroy bone. If the lesion involves the upper jaw, surgical excision may not be possible and while local control is imperative, other therapies have not been fully evaluated. The primary author's personal cat, Gabriella, developed this tumor, with gingival masses around teeth in the upper jaw and evidence of widespread bony destruction of the hard palate. Because of his involvement with Immunophotonics Inc. as an advisor, the author was aware of an in situ autologous cancer vaccine (inCVAX) that is currently under development by the company. One session was performed in a veterinary clinic in Arkansas, and two follow-up sessions at the small animal hospital at the UC Davis veterinary school. No other therapy was provided. As of this writing, 3+ years after first treatment and 3 years, 4 months after presentation, Gabriella is well, with no evidence of disease.

  16. Gene gun delivery systems for cancer vaccine approaches.

    Science.gov (United States)

    Aravindaram, Kandan; Yang, Ning Sun

    2009-01-01

    Gene-based immunization with transgenic DNA vectors expressing tumor-associated antigens (TAA), cytokines, or chemokines, alone or in combination, provides an attractive approach to increase the cytotoxic T cell immunity against various cancer diseases. With this consideration, particle-mediated or gene gun technology has been developed as a nonviral method for gene transfer into various mammalian tissues. It has been shown to induce both humoral and cell-mediated immune responses in both small and large experimental animals. A broad range of somatic cell types, including primary cultures and established cell lines, has been successfully transfected ex vivo or in vitro by gene gun technology, either as suspension or adherent cultures. Here, we show that protocols and techniques for use in gene gun-mediated transgene delivery system for skin vaccination against melanoma using tumor-associated antigen (TAA) human gpl00 and reporter gene assays as experimental systems.

  17. Identification of a microRNA signature in dendritic cell vaccines for cancer immunotherapy

    DEFF Research Database (Denmark)

    Holmstrøm, Kim; Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg

    2010-01-01

    Dendritic cells (DCs) exposed to tumor antigens followed by treatment with T(h)1-polarizing differentiation signals have paved the way for the development of DC-based cancer vaccines. Critical parameters for assessment of the optimal functional state of DCs and prediction of the vaccine potency...

  18. Immunotherapeutic Vaccine as an Alternative Treatment to Overcome Drug-Resistant Ovarian Cancer

    Science.gov (United States)

    2012-07-01

    cells by polyvalent Listeria monocytogenes-based vaccines. J Immunother 32:856-69. 6. Karkada M, Weir, G.M., Quinton,T., Sammatur, L., MacDonald, L.D...polyva- lent Listeria monocytogenes-based vaccines. J Immunother 2009; 32:856–69. 6 Karkada M, Weir GM, Quinton T et al. A novel breast/ovarian cancer

  19. Preventing cervical cancer and genital warts - How much protection is enough for HPV vaccines?

    Science.gov (United States)

    Stanley, Margaret

    2016-07-01

    HPV associated disease is a global health problem: 5.2% of all cancers are HPV associated with HPV 16 and 18 accounting for 70% of cases of cervical cancer. Genital warts caused by HPV 6 and 11 have a lifetime risk of acquisition of 10%. HPV vaccines are subunit vaccines consisting of virus like particles comprised of the L1 major capsid protein. Two vaccines have been licenced since 2006/2007 and are in the National Immunisation programmes in 62 countries. Both vaccines include HPV 16 and 18 VLPs and one also includes HPV 6 and 11. The vaccines are highly immunogenic and well tolerated. Genital HPV is a sexually transmitted infection with peak incidence occurring just after the onset of sexual activity and the routine cohort for immunisation in almost all countries are adolescent girls 9-15 years of age with or without catch up for older adolescents and young women. Population effectiveness is now being demonstrated for these vaccines in countries with high vaccine coverage. HPV vaccines are highly immunogenic and effective and the original 3 dose schedules have already been reduced, for those 14 years and under, to 2 for both licenced vaccines. There is preliminary evidence that 1 dose of vaccine is as effective as 2 or 3 in preventing persistent HPV infection in the cervix in young women and further reductions in dosage may be possible if supported by appropriate virological, immunological and modelling studies.

  20. Society of behavioral medicine supports increasing HPV vaccination uptake: an urgent opportunity for cancer prevention.

    Science.gov (United States)

    Peterson, Caryn E; Dykens, J Andrew; Brewer, Noel T; Buscemi, Joanna; Watson, Karriem; Comer-Hagans, DeLawnia; Ramamonjiarivelo, Zo; Fitzgibbon, Marian

    2016-12-01

    Human papillomavirus (HPV) vaccine coverage remains low in the USA. The Society for Behavioral Medicine (SBM) supports the goals outlined by Healthy People 2020, the President's Cancer Panel, and the National Vaccine Advisory Committee to increase vaccination coverage among both males and females. SBM makes the following recommendations in support of efforts to reduce structural and other barriers to HPV vaccination services in order to increase rates of series completion. We encourage legislators and other policymakers to improve administration authority, insurance coverage, and reimbursement rates to healthcare providers who make the HPV vaccine available to adolescents; provide instrumental support to fund the development of school curricula on HPV vaccination; and increase public awareness that HPV vaccination can prevent cancer. We urge healthcare providers and healthcare systems to increase the strength, quality, and consistency of HPV vaccination recommendations for all eligible patients; to treat HPV vaccination as a routine preventive service; employ culturally appropriate communication strategies in clinical settings to educate eligible patients, parents, and guardians about the importance, effectiveness, and safety of HPV vaccination; and to strengthen and better coordinate the use of electronic medical records and immunization information systems.

  1. Therapeutic cancer vaccine fulfills the promise of immunotherapy in prostate cancer

    OpenAIRE

    Madan, Ravi A; Gulley, James L.

    2011-01-01

    For many years, preclinical and clinical studies have attempted to harness the power of the immune system and focus it on malignant cells in an attempt to improve clinical outcomes for patients with cancer. The current paper describes the landmark phase III trial that led to the first U.S. Food and Drug Administration approval of a therapeutic cancer vaccine. In a randomized trial of 512 patients, those treated with sipuleucel-T survived for 25.8 months compared to those treated with placebo,...

  2. WT1 Peptide Cancer Vaccine for Patients with Hematopoietic Malignancies and Solid Cancers

    Directory of Open Access Journals (Sweden)

    Yoshihiro Oka

    2007-01-01

    Full Text Available Wild-type Wilms' tumor gene WT1 is expressed at a high level in hematopoietic malignancies including acute leukemia, chronic myelogenous leukemia, and myelodysplastic syndromes, as well as in various kinds of solid cancers. Human cytotoxic T lymphocytes (CTLs, which could specifically lyse WT1-expressing tumor cells with HLA class I restriction, were generated in vitro. It was also demonstrated that mice immunized with the WT1 peptide rejected challenges by WT1-expressing cancer cells and survived with no signs of autoaggression to normal organs that physiologically expressed WT1. Furthermore, we and others detected IgM and IgG WT1 antibodies in patients with hematopoietic malignancies, indicating that the WT1 protein was highly immunogenic, and that immunoglobulin class-switch-inducing, WT1-specific, cellular immune responses were elicited in these patients. CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients. These results provided us with the rationale for elicitation of CTL responses targeting the WT1 product for cancer immunotherapy. On the basis of these findings, we performed a phase I clinical trial of a WT1 peptide cancer vaccine for the patients with malignant neoplasms. These results strongly suggested that the WT1 peptide cancer vaccine had efficacy in the clinical setting because clinical responses, including reduction of leukemic blast cells or regression of tumor masses, were observed after the WT1 vaccination in patients with hematopoietic malignancies or solid cancers. The power of a tumor-associated-antigen (TAA-derived cancer vaccine may be enhanced in combination with stronger adjuvants, helper peptide, molecular-target-based drugs, or some chemotherapy drugs, such as gemcitabine, which has been revealed to suppress regulartory T-cell function. In contrast, reduction of WT1 peptide dose may be needed for the treatment of patients with hematological stem cell diseases

  3. A cost-utility analysis of cervical cancer vaccination in preadolescent Canadian females

    Directory of Open Access Journals (Sweden)

    Merid Maraki

    2009-10-01

    Full Text Available Abstract Background Despite the fact that approximately 70% of Canadian women undergo cervical cancer screening at least once every 3 years, approximately 1,300 women were diagnosed with cervical cancer and approximately 380 died from it in 2008. This study estimates the effectiveness and cost-effectiveness of vaccinating 12-year old Canadian females with an AS04-adjuvanted cervical cancer vaccine. The indirect effect of vaccination, via herd immunity, is also estimated. Methods A 12-health-state 1-year-cycle Markov model was developed to estimate lifetime HPV related events for a cohort of 12-year old females. Annual transition probabilities between health-states were derived from published literature and Canadian population statistics. The model was calibrated using Canadian cancer statistics. From a healthcare perspective, the cost-effectiveness of introducing a vaccine with efficacy against HPV-16/18 and evidence of cross-protection against other oncogenic HPV types was evaluated in a population undergoing current screening practices. The base-case analysis included 70% screening coverage, 75% vaccination coverage, $135/dose for vaccine, and 3% discount rate on future costs and health effects. Conservative herd immunity effects were taken into account by estimated HPV incidence using a mathematical model parameterized by reported age-stratified sexual mixing data. Sensitivity analyses were performed to address parameter uncertainties. Results Vaccinating 12-year old females (n = 100,000 was estimated to prevent between 390-633 undiscounted cervical cancer cases (reduction of 47%-77% and 168-275 undiscounted deaths (48%-78% over their lifetime, depending on whether or not herd immunity and cross-protection against other oncogenic HPV types were included. Vaccination was estimated to cost $18,672-$31,687 per QALY-gained, the lower range representing inclusion of cross-protective efficacy and herd immunity. The cost per QALY-gained was most

  4. Preventive vaccines for cervical cancer Vacunas para prevenir el cáncer cervical

    OpenAIRE

    Wheeler, Cosette M.

    1997-01-01

    The potential use of vaccines for the human papillomavirus (HPV) in the prevention and treatment of cervical cancer is a possibility in the near future. Close to 20 genotypes of HPV, of the 75 that have been identified, infect the femine genital tract, but four subtypes (16, 18, 31 and 45) have been associated in close to 80% of cervical cancers. this article proposes that in order to design an effective prophylactic vaccine against HPV infection, an adequate immune response should be guarant...

  5. Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant1

    OpenAIRE

    Overwijk, Willem W; Karin E de Visser; Tirion, Felicia H.; de Jong, Laurina A.; Pols, Thijs W. H.; van der Velden, Yme U; Boorn, Jasper G. van den; Keller, Anna M.; Buurman, Wim A; Theoret, Marc R.; Blom, Bianca; Restifo, Nicholas P.; Kruisbeek, Ada M.; Kastelein, Robert A.; Haanen, John B. A. G.

    2006-01-01

    The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific va...

  6. Natural Killer cells as helper cells in Dendritic cell cancer vaccines

    Directory of Open Access Journals (Sweden)

    María Betina Pampena

    2015-01-01

    Full Text Available Vaccine-based cancer immunotherapy has generated highly variable clinical results due to differing methods of vaccine preparation and variation in patient populations, among other lesser factors. Moreover, these clinical responses do not necessarily correspond with the induction of tumor-specific cytotoxic lymphocytes. Here we review the participation of natural killer (NK cells as alternative immune components that could cooperate in successful vaccination treatment. NK cells have been described as helper cells in dendritic cell-based cancer vaccines, but the role in other kinds of vaccination strategies (whole cells, peptide or DNA- based vaccines is poorly understood. In this article we address the following issues regarding the role of NK cells in cancer vaccines: NK cell anti-tumor action sites, and the loci of NK cell interaction with other immune cells; descriptions of new data on the memory characteristics of NK cells described in infectious diseases; and finally phenotypical and functional changes after vaccination measured by immunomonitoring in preclinical and clinical settings.

  7. Vaccines for established cancer: overcoming the challenges posed by immune evasion.

    Science.gov (United States)

    van der Burg, Sjoerd H; Arens, Ramon; Ossendorp, Ferry; van Hall, Thorbald; Melief, Cornelis J M

    2016-04-01

    Therapeutic vaccines preferentially stimulate T cells against tumour-specific epitopes that are created by DNA mutations or oncogenic viruses. In the setting of premalignant disease, carcinoma in situ or minimal residual disease, therapeutic vaccination can be clinically successful as monotherapy; however, in established cancers, therapeutic vaccines will require co-treatments to overcome immune evasion and to become fully effective. In this Review, we discuss the progress that has been made in overcoming immune evasion controlled by tumour cell-intrinsic factors and the tumour microenvironment. We summarize how therapeutic benefit can be maximized in patients with established cancers by improving vaccine design and by using vaccines to increase the effects of standard chemotherapies, to establish and/or maintain tumour-specific T cells that are re-energized by checkpoint blockade and other therapies, and to sustain the antitumour response of adoptively transferred T cells.

  8. Perspectives on the development of a therapeutic HER-2 cancer vaccine.

    Science.gov (United States)

    Renard, Valéry; Leach, Dana R

    2007-09-27

    With good reason, the majority of cancer vaccines tested, or being tested, have targeted the induction of anti-tumour CTL responses. However, the clinical success of monoclonal antibodies such as Rituximab/CD20, Trastuzumab/HER-2, Cetuximab/EGFR and Bevacisumab/VEGF suggests that their respective targets may also be relevant for cancer vaccines aiming at the induction of an effective humoral anti-tumour response to mimic, or potentially improve upon, the effects of monoclonal therapies. We report here an overview of the development of a protein vaccine targeting HER-2/neu, with an emphasis on the immunologic results obtained from the testing of the vaccine in animal models of disease and in toxicology programs, to its evaluation in three clinical trials in breast cancer patients.

  9. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

    Science.gov (United States)

    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

  10. Recent advances in design of immunogenic and effective naked DNA vaccines against cancer.

    Science.gov (United States)

    Fioretti, Daniela; Iurescia, Sandra; Rinaldi, Monica

    2014-01-01

    A variety of clinical trials for vaccines against cancer have provided evidence that DNA vaccines are well tolerated and have an excellent safety profile. DNA vaccines require much improvement to make them sufficiently effective against cancer in the clinic. Nowadays, it is clear that an increased antigen expression correlates with improved immunogenicity and it is critical to vaccine performance in large animals and humans. Similarly, additional strategies are required to activate effective immunity against poorly immunogenic tumour antigens. This review discusses very recent scientific references focused on the development of sophisticated DNA vaccines against cancer. We report a selection of novel and relevant patents employed to improve their immunogenicity through several strategies such as the use of tissue-specific transcriptional elements, nuclear localisation signalling, codon-optimisation and by targeting antigenic proteins to secretory pathway. Recent patents validating portions or splice variants of tumour antigens as candidates for cancer DNA vaccines with improved specificity, such as mesothelin and hTERT, are also discussed. Lastly, we review novel patents on the use of genetic immunomodulators, such as "universal" T helper epitopes derived from tetanus toxin, E. coli heat labile enterotoxin and vegetable proteins, as well as cytokines, chemokines or costimulatory molecules such as IL-6, IL-15, IL- 21 to amplify immunity against cancer.

  11. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine.

    Science.gov (United States)

    Cheever, Martin A; Higano, Celestia S

    2011-06-01

    Sipuleucel-T (PROVENGE; Dendreon) is the first therapeutic cancer vaccine to be approved by the U.S. Food and Drug Administration. In men who have metastatic castration-resistant prostate cancer with no or minimal symptoms, sipuleucel-T prolongs median survival by 4.1 months compared with results in those treated with placebo. At 3 years, the proportion of patients in the vaccine group who were alive was 50% higher than that in the control group (31.7% versus 21.7%, respectively). Sipuleucel-T, which is designed to elicit an immune response to prostatic acid phosphatase, uses the patient's own immune system to recognize and combat his cancer. Currently, no other agents are available that offer a survival benefit for this population of asymptomatic patients who have not been treated with chemotherapy, except for docetaxel (whose inherent toxicities often lead patients and physicians to delay administration until symptoms develop). Straightforward strategies to increase the efficacy of sipuleucel-T are likely to provide even greater benefit. The preclinical and clinical development of sipuleucel-T is reviewed, and approaches to enhance efficacy are considered herein.

  12. Strategies for Developing Oral Vaccines for Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated Delivery System.

    Science.gov (United States)

    Uddin, Mohammad Nasir; Kouzi, Samir A; Hussain, Muhammad Delwar

    2015-01-01

    Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and

  13. Harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Mayu O Frank

    Full Text Available BACKGROUND: Studies of patients with paraneoplastic neurologic disorders (PND have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC vaccine. METHODS AND FINDINGS: We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002, decrease in prostate specific antigen (PSA slope (p = 0.016, and a two-fold increase in PSA doubling time (p = 0.003 were identified when we compared data before and after vaccination. CONCLUSIONS: An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT00289341.

  14. A prospective highlight on exosomal nanoshuttles and cancer immunotherapy and vaccination

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2015-08-01

    Conclusions: As complex systems, these vesicular micro-/nano-machines convey important cellular messages dependent upon the cells/tissue setting(s. In addition to their potential in diagnosis of cancers, they have been exploited for cancer immunotherapy/vaccination. However, such treatment strategies need to be carefully designed to attain desired clinical outcomes.

  15. Chicken HSP70 DNA vaccine inhibits tumor growth in a canine cancer model.

    Science.gov (United States)

    Yu, Wen-Ying; Chuang, Tien-Fu; Guichard, Cécile; El-Garch, Hanane; Tierny, Dominique; Laio, Albert Taiching; Lin, Ching-Si; Chiou, Kuo-Hao; Tsai, Cheng-Long; Liu, Chen-Hsuan; Li, Wen-Chiuan; Fischer, Laurent; Chu, Rea-Min

    2011-04-18

    Immunization with xenogeneic DNA is a promising cancer treatment to overcome tolerance to self-antigens. Heat shock protein 70 (HSP70) is over-expressed in various kinds of tumors and is believed to be involved in tumor progression. This study tested a xenogeneic chicken HSP70 (chHSP70) DNA vaccine in an experimental canine transmissible venereal tumor (CTVT) model. Three vaccination strategies were compared: the first (PE) was designed to evaluate the prophylactic efficacy of chHSP70 DNA vaccination by delivering the vaccine before tumor inoculation in a prime boost setting, the second (T) was designed to evaluate the therapeutic efficacy of the same prime boost vaccine by vaccinating the dogs after tumor inoculation; the third (PT) was similar to the first strategy (PE), with the exception that the electroporation booster injection was replaced with a transdermal needle-free injection. Tumor growth was notably inhibited only in the PE dogs, in which the vaccination program triggered tumor regression significantly sooner than in control dogs (NT). The CD4(+) subpopulation of tumor-infiltrating lymphocytes and canine HSP70 (caHSP70)-specific IFN-γ-secreting lymphocytes were significantly increased during tumor regression in the PE dogs as compared to control dogs, demonstrating that specific tolerance to caHSP70 has been overcome. In contrast, no benefit of the therapeutic strategy (T) could be noticed and the (PT) strategy only led to partial control of tumor growth. In summary, antitumor prophylactic activity was demonstrated using the chHSP70 DNA vaccine including a boost via electroporation. Our data stressed the importance of DNA electroporation as a booster to get the full benefit of DNA vaccination but also of cancer immunotherapy initiation as early as possible. Xenogeneic chHSP70 DNA vaccination including an electroporation boost is a potential vaccine to HSP70-expressing tumors, although further research is still required to better understand true

  16. The pig as a large preclinical model for therapeutic human anti-cancer vaccine development

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    2016-01-01

    Development of therapeutic cancer vaccines has largely been based on rodent models and the majority failed to establish therapeutic responses in clinical trials. We therefore used pigs as a large animal model for human cancer vaccine development due to the large similarity between the porcine...... and human immunome. We administered peptides derived from porcine IDO, a cancer antigen important in human disease, formulated in Th1-inducing adjuvants to outbred pigs. By in silico prediction 136 candidate IDO-derived peptides were identified and peptide-SLA class I complex stability measurements revealed...

  17. NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Luis E. Fernandez

    2010-01-01

    Full Text Available Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10 and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included.

  18. Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

    Directory of Open Access Journals (Sweden)

    Srinivasan Roopa

    2004-04-01

    Full Text Available Abstract Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective anti-tumor response. Several of these observations are being tested in clinical trials. Immunization with xenogeneic DNA is an attractive approach to treat cancer since it generates T cell and antibody responses. When working in concert, these mechanisms may improve the efficacy of vaccines. The use of xenogeneic DNA in overcoming immune tolerance has been promising not only in inbred mice with transplanted tumors but also in outbred canines, which present with spontaneous tumors, as in the case of human. Use of this strategy also overcomes limitations seen in other types of cancer vaccines. Immunization against defined tumor antigens using a xenogeneic DNA vaccine is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and Non-Hodgkin's Lymphoma.

  19. Immune adjuvants as critical guides directing immunity triggered by therapeutic cancer vaccines.

    Science.gov (United States)

    Schijns, Virgil; Tartour, Eric; Michalek, Jaroslav; Stathopoulos, Apostolos; Dobrovolskienė, Neringa T; Strioga, Marius M

    2014-04-01

    Tumor growth is controlled by natural antitumor immune responses alone or by augmented immune reactivity resulting from different forms of immunotherapy, which has demonstrated clinical benefit in numerous studies, although the overall percentage of patients with durable clinical responses remains limited. This is attributed to the heterogeneity of the disease, the inclusion of late-stage patients with no other treatment options and advanced tumor-associated immunosuppression, which may be consolidated by certain types of chemotherapy. Despite variable responsiveness to distinct types of immunotherapy, therapeutic cancer vaccination has shown meaningful efficacy for a variety of cancers. A key step during cancer vaccination involves the appropriate modeling of the functional state of dendritic cells (DCs) capable of co-delivering four critical signals for proper instruction of tumor antigen-specific T cells. However, the education of DCs, either directly in situ, or ex vivo by various complex procedures, lacks standardization. Also, it is questioned whether ex vivo-prepared DC vaccines are superior to in situ-administered adjuvant-guided vaccines, although both approaches have shown success. Evaluation of these variables is further complicated by a lack of consensus in evaluating vaccination clinical study end points. We discuss the role of signals needed for the preparation of classic in situ and modern ex vivo DC vaccines capable of proper reprogramming of antitumor immune responses in patients with cancer.

  20. The granulocyte macrophage–colony stimulating factor surface modified MB49 bladder cancer stem cells vaccine against metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    2014-07-01

    Full Text Available The MB49 bladder cancer cell vaccine was effective against bladder cancer in the mice model in previous studies. However, part of the tumors regrew as the vaccine could not eliminate the cancer stem cells (CSCs. MB49 bladder cancer stem cells (MCSCs were isolated by a combination of the limited dilution method and the serum free culture medium method. MCSCs possessed higher expression of CD133, CD44, OCT4, NANOG, and ABCG2, the ability of differentiation, higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. Then streptavidin–mouse granulocyte macrophage–colony stimulating factor (SA–mGM–CSF MCSCs vaccine was prepared. SA–mGM–CSF MCSCs vaccine extended the survival of the mice and inhibited the growth of tumor in protective, therapeutic, memorial and specific immune response experiments. The level of immunoglobulin G and the ratio of dendritic cells and CD4+ and CD8+ T cells were highest in the experimental group when compared to those in other four control groups, as well as for the cytotoxicity assay. We demonstrated that SA–mGM–CSF MCSCs vaccine induces an antitumor immune response to metastatic bladder cancer.

  1. HPV infection in cervical and other cancers in Saudi Arabia: implication for prevention and vaccination

    Directory of Open Access Journals (Sweden)

    Ghazi eAlsbeih

    2014-03-01

    Full Text Available HPV is closely associated with cervical cancer that the incidence of this tumor is regarded as a surrogate marker for HPV infection in countries lacking epidemiological studies. HPV is also implicated in subsets of anogenital and oro-pharyngeal cancers. Although cervical cancer is the third most common cancer in women worldwide, its reported incidence is low in Saudi Arabia, ranking number 12 between all cancers in females and accounts only for 2.4% of all new cases, despite the lack of national screening programs. However, the limited available studies from Saudi Arabia indicate that HPV prevalence and genotypes’ distribution in invasive cervical cancer show similar pattern as in the world. Cytology screening (Pap Smear and HPV vaccinations are the two preventive measures against cervical cancer. The two available vaccines are effective against the two most common HPV genotypes (HPV-16 and 18. Since 92% of cervical tumors in the Kingdom are infected with HPV of which 78% are HPV-16 and 18 genotypes, vaccination is expected to protect against more than two-third of cervical cancers in Saudi Arabia. Nevertheless, due to its low incidence (2.1/100,000 women, a proper cost-effectiveness analysis is required to justify the implementation of a costly vaccine bearing in mind that HPV could potentially be associated with about 3% of all cancers. However, further studies are needed to ascertain the real prevalence of HPV at the population level at large, its association with various types of cancers and also the impact of local tradition and emerging behavioral trends that could affect HPV transmission and consequently the effectiveness of applying national vaccination program.

  2. Anti-idiotypic antibodies as cancer vaccines: achievements and future improvements

    Directory of Open Access Journals (Sweden)

    Maha Zohra eLadjemi

    2012-11-01

    Full Text Available Since the discovery of tumor-associated antigens (TAA, researchers have tried to develop immune-based anti-cancer therapies. Thanks to their specificity, monoclonal antibodies (mAbs offer the major advantage to induce fewer side effects than those caused by non-specific conventional treatments (eg. chemotherapy, radiotherapy. Passive immunotherapy by means of mAbs or cytokines has proved efficacy in oncology and validated the use of immune-based agents as part of anti-cancer treatment options. The next step was to try to induce an active immune protection aiming to boost own’s host immune defense against TAAs. Cancer vaccines are thus developed to specifically induce active immune protection targeting only tumor cells while preserving normal tissues from a non-specific toxicity. But, as most of TAAs are self antigens, an immune tolerance against them exists representing a barrier to effective vaccination against these oncoproteins. One promising approach to break this immune tolerance consists in the use of anti-idiotypic mAbs, so called Ab2, as antigen surrogates. This vaccination strategy allows also immunization against non-proteic antigens (such as carbohydrates. In some clinical studies, anti-idiotypic (anti-Id cancer vaccines indeed induced efficient humoral and/or cellular immune responses associated with clinical benefit.This review article will focus on recent achievements of anti-Id mAbs use as cancer vaccines in solid tumors.

  3. Knowledge and acceptability of human papillomavirus vaccination and cervical cancer screening among women in Karnataka, India.

    Science.gov (United States)

    Montgomery, Martha P; Dune, Tanaka; Shetty, Prasanna K; Shetty, Avinash K

    2015-03-01

    Cervical cancer is the leading cause of cancer-related mortality among women in India; however, participation in prevention and screening is low and the reasons for this are not well understood. In a cross-sectional survey in August 2008, 202 healthy women in Karnataka, India completed a questionnaire regarding knowledge, attitudes, and practices related to human papillomavirus (HPV) and cervical cancer. Factors associated with vaccination and Papanicolau (Pap) smear screening acceptance were explored. Thirty-six percent of women had heard of HPV while 15% had heard of cervical cancer. Five percent of women reported ever having a Pap smear, and 4% of women felt at risk of HPV infection. Forty-six percent of women were accepting of vaccination, but fewer (21%) were willing to have a Pap smear. Overall, knowledge related to HPV and cervical cancer topics was low. Women with negative attitudes toward HPV infection were 5.3 (95% confidence interval (CI) 2.8-10) times more likely to accept vaccination but were not significantly more likely to accept Pap smear (odds ratio 1.5, 95% CI 0.7-3.0). Cost and a low level of perceived risk were the most frequent factors cited as potential barriers. Improving awareness of HPV and cervical cancer through health care providers in addition to increasing access to vaccination and screening through government-sponsored programs may be feasible and effective methods to reduce cervical cancer burden in India.

  4. Cost-effectiveness of adding vaccination with the AS04-adjuvanted human papillomavirus 16/18 vaccine to cervical cancer screening in Hungary

    Directory of Open Access Journals (Sweden)

    Vokó Zoltán

    2012-10-01

    Full Text Available Abstract Background The cervical cancer screening program implemented in Hungary to date has not been successful. Along with screening, vaccination is an effective intervention to prevent cervical cancer. The aim of this study was to assess the cost-effectiveness of adding vaccination with the human papillomavirus 16/18 vaccine to the current cervical cancer screening program in Hungary. Methods We developed a cohort simulation state-transition Markov model to model the life course of 12-year-old girls. Eighty percent participation in the HPV vaccination program at 12 years of age was assumed. Transitional probabilities were estimated using data from the literature. Local data were used regarding screening participation rates, and the costs were estimated in US $. We applied the purchasing power parity exchange rate of 129 HUF/$ to the cost data. Only direct health care costs were considered. We used a 3.7% discount rate for both the cost and quality-adjusted life years (QALYs. The time horizon was 88 years. Results Inclusion of HPV vaccination at age 12 in the cervical cancer prevention program was predicted to be cost-effective. The incremental cost-effectiveness ratio (ICER of adding HPV vaccination to the current national cancer screening program was estimated to be 27 588 $/QALY. The results were sensitive to the price of the vaccine, the discount rate, the screening participation rate and whether herd immunity was taken into account. Conclusions Our modeling analysis showed that the vaccination of 12-year-old adolescent girls against cervical cancer with the AS04-adjuvanted human papillomavirus 16/18 vaccine would be a cost-effective strategy to prevent cervical cancer in Hungary.

  5. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....

  6. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...

  7. Human papillomavirus vaccination: the policy debate over the prevention of cervical cancer--a commentary.

    Science.gov (United States)

    Hoops, Katherine E M; Twiggs, Leo B

    2008-07-01

    The human papillomavirus (HPV) family causes a variety of benign, premalignant, and malignant lesions in men and women. HPV types 16 and 18 are responsible for causing 70% of all cases of cervical cancer each year. Recently, a vaccine that can prevent cervical cancer by protecting women from infection with the most common types of HPV has been made available. Following Food and Drug Administration approval and endorsement by the Centers for Disease Control and Prevention, it is the right and the duty of the state legislatures to implement vaccination programs. This vaccine, a vaccine for a sexually transmitted disease, has stirred a fierce debate. Religion and sexuality have dominated the discussion, and political calculations are inherent to the process; nonetheless, epidemiological analyses are also essential to the decision to mandate the HPV vaccine. HPV vaccine program implementation processes are at many stages in many states, and programs vary widely. Some provide information to families, whereas others allot a range of funding for voluntary vaccination. Virginia is, thus far, the only state to have enacted a mandate. This article discusses the various programs in place, the proposed legislation, and the debate surrounding the political process.

  8. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

    Science.gov (United States)

    Luo, Yunping; Zhou, He; Mizutani, Masato; Mizutani, Noriko; Reisfeld, Ralph A.; Xiang, Rong

    2003-07-01

    Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN- and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis. vaccine | tumor | metastases | antiangiogenesis

  9. In situ vaccination: Cancer immunotherapy both personalized and off-the-shelf.

    Science.gov (United States)

    Hammerich, Linda; Binder, Adam; Brody, Joshua D

    2015-12-01

    As cancer immunotherapy continues to benefit from novel approaches which cut immune 'brake pedals' (e.g. anti-PD1 and anti-CTLA4 antibodies) and push immune cell gas pedals (e.g. IL2, and IFNα) there will be increasing need to develop immune 'steering wheels' such as vaccines to guide the immune system specifically toward tumor associated antigens. Two primary hurdles in cancer vaccines have been: identification of universal antigens to be used in 'off-the-shelf' vaccines for common cancers, and 2) logistical hurdles of ex vivo production of individualized whole tumor cell vaccines. Here we summarize approaches using 'in situ vaccination' in which intratumoral administration of off-the-shelf immunomodulators have been developed to specifically induce (or amplify) T cell responses to each patient's individual tumor. Clinical studies have confirmed the induction of systemic immune and clinical responses to such approaches and preclinical models have suggested ways to further potentiate the translation of in situ vaccine trials for our patients.

  10. Human papillomavirus related cervical cancer and anticipated vaccination challenges in Ethiopia.

    Science.gov (United States)

    Gebremariam, TeweldeTesfaye

    2016-01-01

    Cervical cancer is the leading cause of cancer deaths among women in Ethiopia. This may be due to the high prevalence of high-risk human papillomavirus (HR-HPV) genotypes in the population. So far, few studies have been done that showed the presence of HR-HPV genotypes. The HR-HPV-16, -18, -52, -56, -31 and -58 were the most common genotypes reported in Ethiopia. The introduction of HPV vaccines in Ethiopia is likely to go a long way in reducing cervical cancer deaths. However, there are few challenges to the introduction of the vaccines. The target population for HPV vaccination is at the moment not well-defined. Besides, the current HPV vaccines confer only type-specific (HPV-16 and -18) immunity, leaving a small proportion of Ethiopian women unprotected against other HR-HPV genotypes such as 52, 56, 31 and 58. Thus, future HPV vaccines such as the nanovalent vaccine may be more useful to Ethiopia as they will protect women against more genotypes.

  11. Carcinoembryonic antigen (CEA)-based cancer vaccines: recent patents and antitumor effects from experimental models to clinical trials.

    Science.gov (United States)

    Turriziani, Mario; Fantini, Massimo; Benvenuto, Monica; Izzi, Valerio; Masuelli, Laura; Sacchetti, Pamela; Modesti, Andrea; Bei, Roberto

    2012-09-01

    Carcinoembryonic antigen (CEA), a glycosylated protein of MW 180 kDa, is overexpressed in a wide range of human carcinomas, including colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Accordingly, CEA is one of several oncofetal antigens that may serve as a target for active anti-cancer specific immunotherapy. Experimental results obtained by employing animal models have supported the design of clinical trials using a CEA-based vaccine for the treatment of different types of human cancers. This review reports findings from experimental models and clinical evidence on the use of a CEA-based vaccine for the treatment of cancer patients. Among the diverse CEA-based cancer vaccines, DCs- and recombinant viruses-based vaccines seem the most valid. However, although vaccination was shown to induce a strong immune response to CEA, resulting in a delay in tumor progression and prolonged survival in some cancer patients, it failed to eradicate the tumor in most cases, owing partly to the negative effect exerted by the tumor microenvironment on immune response. Thus, in order to develop more efficient and effective cancer vaccines, it is necessary to design new clinical trials combining cancer vaccines with chemotherapy, radiotherapy and drugs which target those factors responsible for immunosuppression of immune cells. This review also discusses relevant patents relating to the use of CEA as a cancer vaccine.

  12. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy.

    Science.gov (United States)

    Fan, Yuchen; Moon, James J

    2015-01-01

    Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  13. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yuchen Fan

    2015-08-01

    Full Text Available Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  14. Dendritic cell-based vaccination in cancer: therapeutic implications emerging from murine models

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    Soledad eMac Keon

    2015-05-01

    Full Text Available Dendritic cells (DCs play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel T there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts towards an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment.

  15. Dendritic Cell-Based Vaccination in Cancer: Therapeutic Implications Emerging from Murine Models

    Science.gov (United States)

    Mac Keon, Soledad; Ruiz, María Sol; Gazzaniga, Silvina; Wainstok, Rosa

    2015-01-01

    Dendritic cells (DCs) play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel-T), there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts toward an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment. PMID:26042126

  16. TAA Polyepitope DNA-Based Vaccines: A Potential Tool for Cancer Therapy

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    Roberto Bei

    2010-01-01

    Full Text Available DNA-based cancer vaccines represent an attractive strategy for inducing immunity to tumor associated antigens (TAAs in cancer patients. The demonstration that the delivery of a recombinant plasmid encoding epitopes can lead to epitope production, processing, and presentation to CD8+ T-lymphocytes, and the advantage of using a single DNA construct encoding multiple epitopes of one or more TAAs to elicit a broad spectrum of cytotoxic T-lymphocytes has encouraged the development of a variety of strategies aimed at increasing immunogenicity of TAA polyepitope DNA-based vaccines. The polyepitope DNA-based cancer vaccine approach can (a circumvent the variability of peptide presentation by tumor cells, (b allow the introduction in the plasmid construct of multiple immunogenic epitopes including heteroclitic epitope versions, and (c permit to enroll patients with different major histocompatibility complex (MHC haplotypes. This review will discuss the rationale for using the TAA polyepitope DNA-based vaccination strategy and recent results corroborating the usefulness of DNA encoding polyepitope vaccines as a potential tool for cancer therapy.

  17. Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine.

    Science.gov (United States)

    Bei, R; Mizejewski, G J

    2011-10-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a poor prognosis and limited therapeutic options. Due to its overexpression in the majority of HCCs, alpha-fetoprotein (AFP) represents one of the most useful markers for hepatocarcinomas and for monitoring patients' response to therapy. Although it was earlier reported that AFP has immunosuppressive properties, it has been recently demonstrated that AFP induces spontaneous T and B cells responses in HCC patients. The characterization of AFP-immunogenic epitopes gives the opportunity to design AFP-based cancer vaccines for human HCC. The activity of AFP-based vaccines has been investigated in HCC mouse models in order to develop novel strategies to treat patients with HCC. This review will discuss the rationale for using the AFP-based vaccination strategy and recent results corroborating the usefulness of AFP vaccines as a potential tool for cancer therapy.

  18. Knowledge of Human Papillomavirus Infection, Cervical Cancer and Willingness to pay for Cervical Cancer Vaccination among Ethnically Diverse Medical Students in Malaysia.

    Science.gov (United States)

    Maharajan, Mari Kannan; Rajiah, Kingston; Num, Kelly Sze Fang; Yong, Ng Jin

    2015-01-01

    The primary objective of this study was to assess the knowledge of medical students and determine variation between different cultural groups. A secondary aim was to find out the willingness to pay for cervical cancer vaccination and the relationships between knowledge and attitudes towards Human Papillomavirus vaccination. A cross-sectional survey was conducted in a private medical university between June 2014 and November 2014 using a convenient sampling method. A total of 305 respondents were recruited and interviewed with standard questionnaires for assessment of knowledge, attitudes and practice towards human papilloma virus and their willingness to pay for HPV vaccination. Knowledge regarding human papilloma virus, human papilloma virus vaccination, cervical cancer screening and cervical cancer risk factors was good. Across the sample, a majority (90%) of the pupils demonstrated a high degree of knowledge about cervical cancer and its vaccination. There were no significant differences between ethnicity and the participants' overall knowledge of HPV infection, Pap smear and cervical cancer vaccination. Some 88% of participants answered that HPV vaccine can prevent cervical cancer, while 81.5% of medical students said they would recommend HPV vaccination to the public although fewer expressed an intention to receive vaccination for themselves.

  19. Preparation of triple-negative breast cancer vaccine through electrofusion with day-3 dendritic cells.

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    Peng Zhang

    Full Text Available Dendritic cells (DCs are professional antigen-presenting cells (APCs in human immune system. DC-based tumor vaccine has met with some success in specific malignancies, inclusive of breast cancer. In this study, we electrofused MDA-MB-231 breast cancer cell line with day-3 DCs derived from peripheral blood monocytes, and explored the biological characteristics of fusion vaccine and its anti-tumor effects in vitro. Day-3 mature DCs were generated from day-2 immature DCs by adding cocktails composed of TNF-α, IL-1β, IL-6 and PEG2. Day-3 mature DCs were identified and electofused with breast cancer cells to generate fusion vaccine. Phenotype of fusion cells were identified by fluorescence microscope and flow cytometer. The fusion vaccine was evaluated for T cell proliferation, secretion of IL-12 and IFN-γ, and induction of tumor-specific CTL response. Despite differences in morphology, day-3 and day-7 DC expressed similar surface markers. The secretion of IL-12 and IFN-γ in fusion vaccine group was much higher than that in the control group. Compared with control group, DC-tumor fusion vaccine could better stimulate the proliferation of allogeneic T lymphocytes and kill more breast cancer cells (MDA-MB-231 in vitro. Day-3 DCs had the same function as the day-7 DCs, but with a shorter culture period. Our findings suggested that day-3 DCs fused with whole apoptotic breast cancer cells could elicit effective specific antitumor T cell responses in vitro and may be developed into a prospective candidate for adoptivet immunotherapy.

  20. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer

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    García-Carrancá Alejandro

    2003-01-01

    Full Text Available Today, "persistent" infections by certain types of human papillomavirus (HPV are considered necessary for developing cervical cancer. Producing efficient vaccines against these viruses may eventually lead to a great reduction in incidence and mortality rates of this cancer. In the case of HPV, the production of traditional vaccines usually based in dead or attenuated viruses is not possible due in part to the lack of systems where large quantities of viral particles could be obtained. Fortunately, the expression of the late L1 protein alone, or in combination with L2, leads to the generation of structures resembling true virions that have been called virus-like particles (VLPs and constitute excellent candidates as prophylactic vaccines. VLPs have shown to be very immunogenic, and have prevented development of natural or challenged infections in both animal systems and humans. Recently, HPV16 VLPs were shown to be very efficient to prevent the development of "persistent" infections, as determined by PCR assays, in a large group of vaccinated women. Therapeutic vaccines, on the other hand, are expected to have an impact on advanced lesions and residual illness, by taking advantaje of the fact that early E6 and E7 genes are thought to be constitutively expressed in cervical tumors and precursor lesions. Finally, DNA-based vaccines could represent a useful alternative for preventing infections by genital HPV.

  1. [Cancer of cervix in Chile. Too much vaccine amid a neglected Papanicolau].

    Science.gov (United States)

    Fica, Alberto

    2014-04-01

    The Chilean Ministry of Health announced the incorporation of a human papillomavirus (HPV) vaccine to prevent cervix uterine cancer (CUC) into the national immunization program during year 2014 This decision was adopted despite of two opposing documents and a significant decrease in cervical cancer associated mortality due to cytological cervical screening. The burden of disease attributed to CUC has declined in Chile and current cost-effectiveness studies should be reviewed considering this decreasing trend, the progressive decrease in coverage rates observed during the past years, the potential need for aditional doses and lower vaccine costs if vaccine is acquired through the PAHO revolving fund. Moreover, serious adverse events associated with these vaccines, which in some countries are more frequent than CUC associated mortality, have not been thoroughly evaluated and are probably underreported. The decision to incorporate the vaccine occurs in a context of progressive weakening of the national cervical screening program leading to a reduced population coverage. This situation jepeordizes the achievements already obtained and poses a challenge to vaccine introduction considering that not all the high-risk viral subtypes are included and thus the risk for CUC does not disappear making cervical screening a vital component of the program that needs to be maintained. This governmental resolution requires a more solid scientific foundation and should not be implemented without resolving current cervical screening shortcomings.

  2. Prophylactic vaccination targeting ERBB3 decreases polyp burden in a mouse model of human colorectal cancer

    Science.gov (United States)

    Bautz, David J.; Sherpa, Ang T.

    2017-01-01

    ABSTRACT Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-ApcMin mice, a model of familial adenomatous polyposis (FAP). In addition, even though they were not vaccinated, ApcMin offspring born to vaccinated females developed significantly fewer polyps than offspring born to control females. Lastly, to validate ERBB as a valid target for vaccination, we found no overt toxicity, increases in apoptosis, or morphological changes in tissues where Erbb3 was ablated in adult mice. These results indicate that prophylactic vaccination targeting ERBB3 could prevent the development of colon polyps in an at-risk patient population.

  3. Prevalence of HPV 16 and 18 and attitudes toward HPV vaccination trials in patients with cervical cancer in Mali

    Science.gov (United States)

    Téguété, Ibrahima; Dolo, Amadou; Sangare, Kotou; Sissoko, Abdoulaye; Rochas, Mali; Beseme, Sarah; Tounkara, Karamoko; Yekta, Shahla; De Groot, Anne S.; Koita, Ousmane A.

    2017-01-01

    Background Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. Aim We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. Methods Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. Results HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. Conclusion This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali. PMID:28231334

  4. Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan

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    Chow Song-Nan

    2010-01-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan. Methods We developed a Markov model to compare the health and economic outcomes of vaccinating preadolescent girls (at the age of 12 years for the prevention of cervical cancer with current practice, including cervical cytological screening. Data were synthesized from published papers or reports, and whenever possible, those specific to Taiwan were used. Sensitivity analyses were performed to account for important uncertainties and different vaccination scenarios. Results Under the assumption that the HPV vaccine could provide lifelong protection, the massive vaccination among preadolescent girls in Taiwan would lead to reduction in 73.3% of the total incident cervical cancer cases and would result in a life expectancy gain of 4.9 days or 8.7 quality-adjusted life days at a cost of US$324 as compared to the current practice. The incremental cost-effectiveness ratio (ICER was US$23,939 per life year gained or US$13,674 per quality-adjusted life year (QALY gained given the discount rate of 3%. Sensitivity analyses showed that this ICER would remain below US$30,000 per QALY under most conditions, even when vaccine efficacy was suboptimal or when vaccine-induced immunity required booster shots every 13 years. Conclusions Although gains in life expectancy may be modest at the individual level, the results indicate that prophylactic HPV vaccination of preadolescent girls in Taiwan would result in substantial population benefits with a favorable cost

  5. The human papillomavirus vaccine: A powerful tool for the primary prevention of cervical cancer.

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    Nubia Muñoz

    2009-11-01

    Full Text Available Prophylactic human papillomavirus (HPV vaccine is the most promissory public health tool for primary prevention of cervical cancer. Immunization of females before the acquisition of HPV infection has the greatest impact in preventing pre-neoplasic lesions and cervical cancer. Current HPV vaccines do not eliminate cervical cancer risk, therefore, screening should continue covering vaccinated as well as women that do not get the vaccine. The strategies that include combination of high-coverage vaccination of HPV-unexposed adolescents with screening using methods with higher sensitivity than cytology as HPV test may be more cost-effective than the strategies currently used. The cytology-based screening programs of Latin America countries including Colombia are very ineffective. The evidence in favor of the cost-effectiveness of other screening strategies such as HPV tests and visual inspection followed by immediate treatment for women with difficult access to health care services in developing countries warrants the immediate revision of the current strategies.

  6. Humoral Immune Response to Keyhole Limpet Haemocyanin, the Protein Carrier in Cancer Vaccines

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    A. Kantele

    2011-01-01

    Full Text Available Keyhole limpet haemocyanin (KLH appears to be a promising protein carrier for tumor antigens in numerous cancer vaccine candidates. The humoral immune response to KLH was characterized at the single-cell level with ELISPOT combined with separations of cell populations according to their expression of homing receptors (HRs. The analysis of HR expressions is expected to reveal the targeting of the immune response in the body. Eight orally primed and four nonprimed volunteers received KLH-vaccine subcutaneously. Circulating KLH-specific plasmablasts were found in all volunteers, 60 KLH-specific plasmablasts/106 PBMC in the nonprimed and 136/106 in the primed group. The proportion of L-selectin+ plasmablasts proved high and integrin α4β7+ low. KLH serving as protein carrier in several vaccines, the homing profile of KLH-specific response may be applicable to the cancer antigen parts in the same vaccines. The present data reflect a systemic homing profile, which appears advantageous for the targeting of immune response to cancer vaccines.

  7. Exploring the cost-effectiveness of HPV vaccination in Vietnam: insights for evidence-based cervical cancer prevention policy.

    Science.gov (United States)

    Kim, Jane J; Kobus, Katie E; Diaz, Mireia; O'Shea, Meredith; Van Minh, Hoang; Goldie, Sue J

    2008-07-29

    Using mathematical models of cervical cancer for the northern and southern regions of Vietnam, we assessed the cost-effectiveness of cervical cancer prevention strategies and the tradeoffs between a national and region-based policy in Vietnam. With 70% vaccination and screening coverage, lifetime risk of cancer was reduced by 20.4-76.1% with vaccination of pre-adolescent girls and/or screening of older women. Only when the cost per vaccinated girl was low (i.e., I$100), screening alone was most cost-effective. When optimal policies differed between regions, implementing a national strategy resulted in health and economic inefficiencies. HPV vaccination appears to be an attractive cervical cancer prevention strategy for Vietnam, provided high coverage can be achieved in young pre-adolescent girls, cost per vaccinated girl is

  8. Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer.

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    Li, Jinming; Sun, Yanli; Jia, Tingting; Zhang, Rui; Zhang, Kuo; Wang, Lunan

    2014-04-01

    Prostate cancer (PCa) is the most diagnosed cancer in the western male population with high mortality. Recently, alternative approaches based on immunotherapy including mRNA vaccines for PCa have shown therapeutic promise. However, for mRNA vaccine, several disadvantages such as the instability of mRNA, the high cost of gold particles, the limited production scale for mRNA-transfected dendritic cells in vitro, limit their development. Herein, recombinant bacteriophage MS2 virus-like particles (VLPs), which based on the interaction of a 19-nucleotide RNA aptamer and the coat protein of bacteriophage MS2, successfully addressed these questions, in which target mRNA was packaged by MS2 capsid. MS2 VLP-based mRNA vaccines were easily prepared by recombinant protein technology, nontoxic and RNase-resistant. We show the packaged mRNA was translated into protein as early as 12 hr after phagocytosed by macrophages. Moreover, MS2 VLP-based mRNA vaccines induced strong humoral and cellular immune responses, especially antigen-specific cytotoxic T-lymphocyte (CTL) and balanced Th1/Th2 responses without upregulation of CD4(+) regulatory T cells, and protected C57BL/6 mice against PCa completely. As a therapeutic vaccine, MS2 VLP-based mRNA vaccines delayed tumor growth. Our results provide proof of concept on the efficacy and safety of MS2 VLP-based mRNA vaccine, which provides a new delivery approach for mRNA vaccine and implies important clinical value for the prevention and therapy of PCa.

  9. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    single antigen such as HER2 in breast cancer is likely to be insufficient - instead we need a repertoire of multiple immunologically validated T cell...Award Number: W81XWH-11-1-0548 TITLE: Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer PRINCIPAL INVESTIGATOR...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection

  10. Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

    Science.gov (United States)

    2008-09-01

    CYP1B1 ), each overexpressed in >90% of invasive breast cancers but rarely found in normal tissue -- may fill this gap. Such targets, if found at...hTERT and CYP1B1 provide an opportunity for both early detection and cancer vaccination. Objective/Hypothesis: We hypothesize that immunologic responses...in ductal lavage fluid from BRCA1 and BRCA2 mutation carriers The last year has been spent studying genetic polymorphisms in BRCA1 and BRCA2

  11. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  12. Cervical cancer screening in partly HPV vaccinated cohorts - A cost-effectiveness analysis

    NARCIS (Netherlands)

    S.K. Naber (Steffie); S.M. Matthijsse (Suzette); K. Rozemeijer (Kirsten); C. Penning (Corine); I.M.C.M. de Kok (Inge); M. van Ballegooijen (Marjolein)

    2016-01-01

    textabstractBackground: Vaccination against the oncogenic human papillomavirus (HPV) types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable) herd effect will be limited at first, but is expected to increase over t

  13. RhoC a new target for therapeutic vaccination against metastatic cancer

    DEFF Research Database (Denmark)

    Wenandy, L.; Sorensen, R.B.; Straten, P.T.

    2008-01-01

    Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...

  14. Cervical Cancer Screening in Partly HPV Vaccinated Cohorts - A Cost-Effectiveness Analysis.

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    Steffie K Naber

    Full Text Available Vaccination against the oncogenic human papillomavirus (HPV types 16 and 18 will reduce the prevalence of these types, thereby also reducing cervical cancer risk in unvaccinated women. This (measurable herd effect will be limited at first, but is expected to increase over time. At a certain herd immunity level, tailoring screening to vaccination status may no longer be worth the additional effort. Moreover, uniform screening may be the only viable option. We therefore investigated at what level of herd immunity it is cost-effective to also reduce screening intensity in unvaccinated women.We used the MISCAN-Cervix model to determine the optimal screening strategy for a pre-vaccination population and for vaccinated women (~80% decreased risk, assuming a willingness-to-pay of €50,000 per quality-adjusted life year gained. We considered HPV testing, cytology testing and co-testing and varied the start age of screening, the screening interval and the number of lifetime screens. We then calculated the incremental cost-effectiveness ratio (ICER of screening unvaccinated women with the strategy optimized to the pre-vaccination population as compared to with the strategy optimized to vaccinated women, assuming different herd immunity levels.Primary HPV screening with cytology triage was the optimal strategy, with 8 lifetime screens for the pre-vaccination population and 3 for vaccinated women. The ICER of screening unvaccinated women 8 times instead of 3 was €28,085 in the absence of herd immunity. At around 50% herd immunity, the ICER reached €50,000.From a herd immunity level of 50% onwards, screening intensity based on the pre-vaccination risk level becomes cost-ineffective for unvaccinated women. Reducing the screening intensity of uniform screening may then be considered.

  15. Are Older Adults Up-to-Date With Cancer Screening and Vaccinations?

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    Douglas Shenson, MD, MPH, MS

    2005-07-01

    Full Text Available Introduction Public health organizations in the United States emphasize the importance of providing routine screening for breast cancer, cervical cancer, and colorectal cancer, as well as vaccinations against influenza and pneumococcal disease among older adults. We report a composite measure of adults aged 50 years and older who receive recommended cancer screening services and vaccinations. Methods We analyzed state data from the 2002 Behavioral Risk Factor Surveillance System, which included 105,860 respondents aged 50 and older. We created a composite measure that included colonoscopy or sigmoidoscopy within 10 years or a fecal occult blood test in the past year, an influenza vaccination in the past year, a Papanicolaou test within 3 years for women with an intact cervix, a mammogram, and for adults aged 65 and older, a pneumonia vaccination during their lifetime. We performed separate analyses for four age and sex groups: men aged 50 to 64, women aged 50 to 64, men aged 65 and older, and women aged 65 and older. Results The percentage of each age and sex group that was up-to-date according to our composite measure ranged from 21.1% of women aged 50 to 64 (four tests to 39.6% of men aged 65 and older (three tests. For each group, results varied by income, education, race/ethnicity, insurance status, and whether the respondent had a personal physician. Conclusion These results suggest the need to improve the delivery of cancer screenings and vaccinations among adults aged 50 and older. We propose continued efforts to measure use of clinical preventive services.

  16. Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses.

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    Ruanne V Barnabas

    2006-05-01

    Full Text Available BACKGROUND: Candidate human papillomavirus (HPV vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. METHODS AND FINDINGS: We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation and high (90% in a national immunisation programme coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16 cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has the potential to

  17. Vulval cancer and HPV vaccination in recurrent disease

    DEFF Research Database (Denmark)

    Gustafson, L W; Gade, Melina; Blaakær, Jan

    2014-01-01

    KEY CLINICAL MESSAGE: A woman diagnosed with a recurrent vulval carcinoma after initial treatment with radiochemotherapy is presented. After three additional relapses she was vaccinated with Gardasil. She has had no relapses in her vulvar area for 39 months and an overall progression-free survival...

  18. Effect of 25-Hydroxyvitamin D Status on Serological Response to Influenza Vaccine in Prostate Cancer Patients

    Science.gov (United States)

    Chadha, Manpreet K.; Fakih, Marwan; Muindi, Josephia; Tian, Lili; Mashtare, Terry; Johnson, Candace S.; Trump, Donald

    2015-01-01

    BACKGROUND Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS During the 2006–2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006–2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16–71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine. PMID:20812224

  19. Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

    Science.gov (United States)

    Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

    2015-04-10

    Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination.

  20. Immunotherapy and therapeutic vaccines in prostate cancer:an update on current strategies and clinical implications

    Institute of Scientific and Technical Information of China (English)

    B Harpreet Singh; James L Gulley

    2014-01-01

    In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical beneift.

  1. Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications

    Directory of Open Access Journals (Sweden)

    B Harpreet Singh

    2014-06-01

    Full Text Available In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

  2. Immune Suppression in Tumors as a Surmountable Obstacle to Clinical Efficacy of Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Wieërs, Grégoire; Demotte, Nathalie; Godelaine, Danièle; Bruggen, Pierre van der, E-mail: pierre.vanderbruggen@bru.licr.org [Ludwig Institute for Cancer Research and Université catholique de Louvain, de Duve Institute, 74 av. Hippocrate, P.O. Box B1-7403, B-1200 Brussels (Belgium)

    2011-07-18

    Human tumors are usually not spontaneously eliminated by the immune system and therapeutic vaccination of cancer patients with defined antigens is followed by tumor regressions only in a small minority of the patients. The poor vaccination effectiveness could be explained by an immunosuppressive tumor microenvironment. Because T cells that infiltrate tumor metastases have an impaired ability to lyse target cells or to secrete cytokine, many researchers are trying to decipher the underlying immunosuppressive mechanisms. We will review these here, in particular those considered as potential therapeutic targets. A special attention will be given to galectins, a family of carbohydrate binding proteins. These lectins have often been implicated in inflammation and cancer and may be useful targets for the development of new anti-cancer therapies.

  3. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer.

    Science.gov (United States)

    Odunsi, Kunle; Matsuzaki, Junko; James, Smitha R; Mhawech-Fauceglia, Paulette; Tsuji, Takemasa; Miller, Austin; Zhang, Wa; Akers, Stacey N; Griffiths, Elizabeth A; Miliotto, Anthony; Beck, Amy; Batt, Carl A; Ritter, Gerd; Lele, Shashikant; Gnjatic, Sacha; Karpf, Adam R

    2014-01-01

    The cancer-testis/cancer-germline antigen NY-ESO-1 is a vaccine target in epithelial ovarian cancer (EOC), but its limited expression is a barrier to vaccine efficacy. As NY-ESO-1 is regulated by DNA methylation, we hypothesized that DNA methyltransferase (DNMT) inhibitors may augment NY-ESO-1 vaccine therapy. In agreement, global DNA hypomethylation in EOC was associated with the presence of circulating antibodies to NY-ESO-1. Pre-clinical studies using EOC cell lines showed that decitabine treatment enhanced both NY-ESO-1 expression and NY-ESO-1-specific CTL-mediated responses. Based on these observations, we performed a phase I dose-escalation trial of decitabine, as an addition to NY-ESO-1 vaccine and doxorubicin liposome (doxorubicin) chemotherapy, in 12 patients with relapsed EOC. The regimen was safe, with limited and clinically manageable toxicities. Both global and promoter-specific DNA hypomethylation occurred in blood and circulating DNAs, the latter of which may reflect tumor cell responses. Increased NY-ESO-1 serum antibodies and T cell responses were observed in the majority of patients, and antibody spreading to additional tumor antigens was also observed. Finally, disease stabilization or partial clinical response occurred in 6/10 evaluable patients. Based on these encouraging results, evaluation of similar combinatorial chemo-immunotherapy regimens in EOC and other tumor types is warranted.

  4. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  5. Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    João Henrique Campos

    2015-01-01

    Full Text Available Almost all cells and organisms release membrane structures containing proteins, lipids, and nucleic acids called extracellular vesicles (EVs, which have a wide range of functions concerning intercellular communication and signaling events. Recently, the characterization and understanding of their biological role have become a main research area due to their potential role in vaccination, as biomarkers antigens, early diagnostic tools, and therapeutic applications. Here, we will overview the recent advances and studies of Evs shed by tumor cells, bacteria, parasites, and fungi, focusing on their inflammatory role and their potential use in vaccination and diagnostic of cancer and infectious diseases.

  6. Immunogenicity and clinical effectiveness of the trivalent inactivated influenza vaccine in immunocompromised children undergoing treatment for cancer.

    Science.gov (United States)

    Kotecha, Rishi S; Wadia, Ushma D; Jacoby, Peter; Ryan, Anne L; Blyth, Christopher C; Keil, Anthony D; Gottardo, Nicholas G; Cole, Catherine H; Barr, Ian G; Richmond, Peter C

    2016-02-01

    Influenza is associated with significant morbidity and mortality in children receiving therapy for cancer, yet recommendation for, and uptake of the seasonal vaccine remains poor. One hundred children undergoing treatment for cancer were vaccinated with the trivalent inactivated influenza vaccine according to national guidelines in 2010 and 2011. Influenza-specific hemagglutinin inhibition antibody titers were performed on blood samples taken prior to each vaccination and 4 weeks following the final vaccination. A nasopharyngeal aspirate for influenza was performed on all children who developed an influenza-like illness. Following vaccination, seroprotection and seroconversion rates were 55 and 43% for H3N2, 61 and 43% for H1N1, and 41 and 33% for B strain, respectively. Overall, there was a significant geometric mean fold increase to H3N2 (GMFI 4.56, 95% CI 3.19-6.52, P children with solid compared with hematological malignancies and in children vaccinated study population, compared with 6.8% in unvaccinated controls, providing an adjusted estimated vaccine effectiveness of 72% (95% CI -26-94%). There were no serious adverse events and a low reactogenicity rate of 3%. The trivalent inactivated influenza vaccine is safe, immunogenic, provides clinical protection and should be administered annually to immunosuppressed children receiving treatment for cancer. All children <10 years of age should receive a two-dose schedule.

  7. Long-term clinical and immunological effects of p53-SLP (R) vaccine in patients with ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Vermeij, Renee; Hoogeboom, Baukje-Nynke; Schulze, Ute R.; Wolf, Rinze; Hamming, Ineke E.; van der Zee, Ate G.; Melief, Kees J.; van der Burg, Sjoerd H.; Daemen, Toos; Nijman, Hans W.

    2012-01-01

    Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in patients with small cell lung cancer. We investigated long-term clinical and immunological effects of the p53-synthetic long peptide (p53-SLP (R)) vaccine in pa

  8. Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer

    Science.gov (United States)

    Stewart Massad, L.; Evans, Charlesnika T.; Weber, Kathleen M.; D'Souza, Gypsyamber; Hessol, Nancy A.; Wright, Rodney L.; Colie, Christine; Strickler, Howard D.; Wilson, Tracey E.

    2015-01-01

    Purpose To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. Methods In 2007, 2008–9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. Results In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0–24) increased from 2007 (12.8, S.D. 5.8) to 2008–9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D. 5.2, P < 0.0001 vs 2007 and < 0.04 vs 2008–9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline. Conclusion Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding. PMID:25870859

  9. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

    Science.gov (United States)

    1998-07-01

    In: Cancer: Principles and Practice of Oncology . DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB Lippincott Co., Philadelphia, p. 293, 1993. 2...Alteration of signal transduction in T cells from cancer patients. In: Important Advances in Oncology 1995. DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB...Rosenberg SA: Cell transfer therapy: Clinical applications. In: Biologic Therapy of Cancer. DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB Lippincott

  10. Development of an autologous canine cancer vaccine system for resectable malignant tumors in dogs.

    Science.gov (United States)

    Yannelli, J R; Wouda, R; Masterson, T J; Avdiushko, M G; Cohen, D A

    2016-12-01

    While conventional therapies exist for canine cancer, immunotherapies need to be further explored and applied to the canine setting. We have developed an autologous cancer vaccine (K9-ACV), which is available for all dogs with resectable disease. K9-ACV was evaluated for safety and immunogenicity for a variety of cancer types in a cohort of companion dogs under veterinary care. The autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies. The resultant single cell suspensions were then UV-irradiated resulting in immunogenic cell death of the tumor cells. Following sterility and endotoxin testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the participating veterinary clinics. The treating veterinarians then vaccinated each patient with three intradermal injections (10 million cells per dose) at 30-day intervals (one prime and two boost injections). In a cohort of 20 dogs completing the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor antigens as demonstrated using western blot analysis of pre- and post-peripheral blood samples. We also report several dogs have lived beyond expected survival time based on previously published data. In summary, K9-ACV is an additional option to be considered for the treatment of dogs with resectable cancer.

  11. Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

    Directory of Open Access Journals (Sweden)

    Holly J Corbett

    Full Text Available BACKGROUND: Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™ as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV vaccine (Gardasil® commonly used as a prophylactic vaccine against cervical cancer. METHODOLOGY/PRINCIPAL FINDINGS: Micro-projection arrays dry-coated with vaccine material (Gardasil® delivered to C57BL/6 mouse ear skin released vaccine within 5 minutes. To assess vaccine immunogenicity, doses of corresponding to HPV-16 component of the vaccine between 0.43 ± 0.084 ng and 300 ± 120 ng (mean ± SD were administered to mice at day 0 and day 14. A dose of 55 ± 6.0 ng delivered intracutaneously by micro-projection array was sufficient to produce a maximal virus neutralizing serum antibody response at day 28 post vaccination. Neutralizing antibody titres were sustained out to 16 weeks post vaccination, and, for comparable doses of vaccine, somewhat higher titres were observed with intracutaneous patch delivery than with intramuscular delivery with the needle and syringe at this time point. CONCLUSIONS/SIGNIFICANCE: Use of dry micro-projection arrays (Nanopatch™ has the potential to overcome the need for a vaccine cold chain for common vaccines currently delivered by needle and syringe, and to reduce risk of needle-stick injury and vaccine avoidance due to the fear of the needle especially among children.

  12. Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination.

    Science.gov (United States)

    Kawada, Junji; Wada, Hisashi; Isobe, Midori; Gnjatic, Sacha; Nishikawa, Hiroyoshi; Jungbluth, Achim A; Okazaki, Nami; Uenaka, Akiko; Nakamura, Yurika; Fujiwara, Shinichi; Mizuno, Naoaki; Saika, Takashi; Ritter, Erika; Yamasaki, Makoto; Miyata, Hiroshi; Ritter, Gerd; Murphy, Roger; Venhaus, Ralph; Pan, Linda; Old, Lloyd J; Doki, Yuichiro; Nakayama, Eiichi

    2012-02-01

    NY-ESO-1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY-ESO-1-expressing tumors with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and showed efficient induction of NY-ESO-1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE-A1, MAGE-A3, MAGE-A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme-linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription-polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY-ESO-1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6-tag and/or bacterial products included in a preparation of CHP-NY-ESO-1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine.

  13. Fueling the engine and releasing the break:combinational therapy of cancer vaccines and immune checkpoint inhibitors

    Institute of Scientific and Technical Information of China (English)

    Jennifer Kleponis; Richard Skelton; Lei Zheng

    2015-01-01

    Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-inifltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.

  14. The Consequence of Immune Suppressive Cells in the Use of Therapeutic Cancer Vaccines and Their Importance in Immune Monitoring

    Directory of Open Access Journals (Sweden)

    Matteo Vergati

    2011-01-01

    Full Text Available Evaluating the number, phenotypic characteristics, and function of immunosuppressive cells in the tumor microenvironment and peripheral blood could elucidate the antitumor immune response and provide information to evaluate the efficacy of cancer vaccines. Further studies are needed to evaluate the correlation between changes in immunosuppressive cells and clinical outcomes of patients in cancer vaccine clinical trials. This paper focuses on the role of T-regulatory cells, myeloid-derived suppressor cells, and tumor-associated macrophages in cancer and cancer immunotherapy and their role in immune monitoring.

  15. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    Science.gov (United States)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  16. Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

    Science.gov (United States)

    Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A

    2016-10-01

    Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

  17. Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

    DEFF Research Database (Denmark)

    Kyte, Jon Amund; Trachsel, Sissel; Risberg, Bente

    2009-01-01

    Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses......-delineation applies to cancer vaccine responses. T cell clones were generated from all nine patients studied. We find that surviving patients harbor durable tumor-specific responses against vaccine antigens from telomerase, RAS or TGFbeta receptor II. Analyses of consecutive samples suggest that booster...

  18. Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand

    Directory of Open Access Journals (Sweden)

    Teerawattananon Yot

    2010-07-01

    Full Text Available Abstract Background Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand. Methods In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions. Results Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country’s political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country’s political crisis, the MoPH’s campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target. Conclusion The Thai case study suggests that the political crisis was a

  19. The pig as a model for therapeutic human anti-cancer vaccine development, elucidating the T-cell reactivity against IDO and RhoC

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    Immunotherapy against cancer has shown increased overall survival of metastatic cancer patients and is a promising new vaccine target. For this to succeed, appropriate tailoring of vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses towards co-delivered cancer antigens...... is important. Previous development of therapeutic cancer vaccines has largely been based on studies in mice and the majority of these candidate vaccines failed to establish therapeutic responses in subsequent human clinical trials. Since the porcine immunome is more closely related to the human counterpart, we...... here introduce pigs as a superior large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, both known to be important in human cancer development and progression, were used as vaccine targets. Pigs were...

  20. Immune Monitoring in Cancer Vaccine Clinical Trials: Critical Issues of Functional Flow Cytometry-Based Assays

    OpenAIRE

    Iole Macchia; Francesca Urbani; Enrico Proietti

    2013-01-01

    The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometr...

  1. Synergy of SOCS-1 Inhibition and Microbial-Based Cancer Vaccines

    Science.gov (United States)

    2014-11-01

    pathogen Listeria monocytogenes to promote a tumor-specific immune response while concurrently removing the brakes from a portion of the immune system...1S. SUBJECT TERMS T Cells, Listeria monocytogenes, cancer vaccines 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a. NAME OF...12 FINAL REPORT PI: Bahjat, Keith INTRODUCTION We have been working with live-­‐‑attenuated Listeria (L

  2. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines.

    Science.gov (United States)

    Dohnal, Alexander Michael; Graffi, Sebastian; Witt, Volker; Eichstill, Christina; Wagner, Dagmar; Ul-Haq, Sidrah; Wimmer, Doris; Felzmann, Thomas

    2009-01-01

    Manufacturing procedures for cellular therapies are continuously improved with particular emphasis on product safety. We previously developed a dendritic cell (DC) cancer vaccine technology platform that uses clinical grade lipopolysaccharide (LPS) and interferon (IFN)-y for the maturation of monocyte derived DCs. DCs are frozen after 6 hrs exposure at a semi-mature stage (smDCs) retaining the capacity to secret interleukin (IL)-12 and thus support cytolytic T-cell responses, which is lost at full maturation. We compared closed systems for monocyte enrichment from leucocyte apheresis products from healthy individuals using plastic adherence, CD14 selection, or CD2/19 depletion with magnetic beads, or counter flow centrifugation (elutriation) using a clinical grade in comparison to a research grade culture medium for the following DC generation. We found that elutriation was superior compared to the other methods showing 36 +/- 4% recovery, which was approximately 5-fold higher as the most frequently used adherence protocol (8 +/- 1%), and a very good purity (92 +/- 5%) of smDCs. Immune phenotype and IL-12 secretion (adherence: 1.4 +/- 0.4; selection: 20 +/- 0.6; depletion: 1 +/-0.5; elutriation: 3.6 +/- 1.5 ng/ml) as well as the potency of all DCs to stimulate T cells in an allogeneic mixed leucocyte reaction did not show statistically significant differences. Research grade and clinical grade DC culture media were equally potent and freezing did not impair the functions of smDCs. Finally, we assessed the functional capacity of DC cancer vaccines manufactured for three patients using this optimized procedure thereby demonstrating the feasibility of manufacturing DC cancer vaccines that secret IL-12 (9.4 +/- 6.4 ng/ml). We conclude that significant steps were taken here towards clinical grade DC cancer vaccine manufacturing.

  3. Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

    Science.gov (United States)

    2015-09-01

    biospecimens followed protocols approved by the Institutional Review Board of Memorial Sloan Kettering Cancer Center (MSKCC). Leukocyte concentrates...Antitumor Immunity and Checkpoint Immunotherapy. Cancer immunology research 2, 926-936 (2014). 17. Wherry, E.J. T cell exhaustion. Nat Immunol 12, 492... Cancer Vaccine Therapy PRINCIPAL INVESTIGATOR: David J. Chung, MD, PhD CONTRACTING ORGANIZATION: Sloan-Kettering Institute for Cancer Research New

  4. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  5. Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

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    Chen Hui-Ming

    2012-04-01

    Full Text Available Abstract Background Shikonin, a phytochemical purified from Lithospermum erythrorhizon, has been shown to confer diverse pharmacological activities, including accelerating granuloma formation, wound healing, anti-inflammation and others, and is explored for immune-modifier activities for vaccination in this study. Transdermal gene-based vaccine is an attractive approach for delivery of DNA transgenes encoding specific tumor antigens to host skin tissues. Skin dendritic cells (DCs, a potent antigen-presenting cell type, is known to play a critical role in transmitting and orchestrating tumor antigen-specific immunities against cancers. The present study hence employs these various components for experimentation. Method The mRNA and protein expression of RANTES were detected by RT-PCR and ELISA, respectively. The regional expression of RANTES and tissue damage in test skin were evaluated via immunohistochemistry assay. Fluorescein isothiocyanate sensitization assay was performed to trace the trafficking of DCs from the skin vaccination site to draining lymph nodes. Adjuvantic effect of shikonin on gene gun-delivered human gp100 (hgp100 DNA cancer vaccine was studied in a human gp100-transfected B16 (B16/hgp100 tumor model. Results Among various phytochemicals tested, shikonin induced the highest level of expression of RANTES in normal skin tissues. In comparison, mouse RANTES cDNA gene transfection induced a higher level of mRANTES expression for a longer period, but caused more extensive skin damage. Topical application of shikonin onto the immunization site before gene gun-mediated vaccination augmented the population of skin DCs migrating into the draining lymph nodes. A hgp100 cDNA gene vaccination regimen with shikonin pretreatment as an adjuvant in a B16/hgp100 tumor model increased cytotoxic T lymphocyte activities in splenocytes and lymph node cells on target tumor cells. Conclusion Together, our findings suggest that shikonin can

  6. Immunotherapy for the treatment of breast cancer: checkpoint blockade, cancer vaccines, and future directions in combination immunotherapy.

    Science.gov (United States)

    McArthur, Heather L; Page, David B

    2016-11-01

    Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers. Specifically, overall response rates of 19% with PD-1/PD-L1-directed antibodies have been reported in 2 small studies of women with PD-L1-positive, heavily pretreated advanced triple-negative breast cancer. In combination with nab-paclitaxel, confirmed response rates were 46% in a PD-L1-unselected population in the first-line metastatic triple-negative breast cancer setting. Checkpoint-blocking antibodies also have been evaluated in small studies of women with hormone receptor-positive metastatic breast cancer, and in women whose breast cancers lack PD-L1 expression, with more modest response rates. It has been hypothesized that some breast cancers are not inherently recognized by the immune system; however, preclinical and preliminary clinical data suggest that inherently modest immunogenicity may be overcome with novel vaccination strategies, as well as strategies that combine immune checkpoint blockade with methods of optimizing antigen presentation, such as tumor ablation, radiation, chemotherapy, or other approaches. If ongoing registrational trials support the use of immunotherapy, it could revolutionize the care of early-stage and metastatic breast cancer, and ideally improve cure rates.

  7. Cervical cancer vaccine: Exploring new opportunities and challenges for developing countries

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    Ananya Ray Laskar

    2011-01-01

    Full Text Available Cervical cancer is the second most common cancer in women worldwide, and the burden of the disease is disproportionately high in the developing world (>80%. With the advent of two new vaccines, "Gardasil" developed by Merck & Co. New Jersey, USA and "Cervarix" developed by GlaxoSmithKline (GSK in Philadelphia, USA, the future holds newer promises for prevention and control of the disease. However, various regulatory and policy changes also may be required to be undertaken and the various new challenges need to be addressed.

  8. Perceptions of Nigerian Women about Human Papilloma Virus, Cervical Cancer, and HPV Vaccine.

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    Akanbi, Olusola Anuoluwapo; Iyanda, Abiodun; Osundare, Folakemi; Opaleye, Oluyinka Oladele

    2015-01-01

    Background. Cervical cancer caused by human papilloma virus (HPV) though preventable has claimed the lives of many women worldwide. This study was embarked upon to evaluate the general knowledge and perceptions of Nigerian women on HPV, cervical cancer, and HPV vaccine. Methods. Structured questionnaires were administered to a cross section of 737 women randomly selected from the general population in two southwestern States of Nigeria. Statistical analysis was done using SPSS computer software version 16. A P value >0.05 was considered statistically significant. Results. One hundred and seventy-six (23.9%) of the respondents had knowledge of HPV; 474 (64.3%) are aware of cervical cancer but only 136 (18.5%) know that HPV causes cervical cancer. 200 (27.1%) are aware that there is an HPV vaccine while 300 (40.7%) had knowledge of Pap smear test. Two hundred and sixty (35.3%) of the respondents know that early detection of HPV can prevent cervical cancer and in spite of this, only 110 (14.9%) have taken the Pap smear test before while 151 (20.5%) are not willing to go for the test at all. Conclusions. There is therefore the need to create proper awareness on the HPV and its possible consequence of cervical carcinoma.

  9. Perceptions of Nigerian Women about Human Papilloma Virus, Cervical Cancer, and HPV Vaccine

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    Olusola Anuoluwapo Akanbi

    2015-01-01

    Full Text Available Background. Cervical cancer caused by human papilloma virus (HPV though preventable has claimed the lives of many women worldwide. This study was embarked upon to evaluate the general knowledge and perceptions of Nigerian women on HPV, cervical cancer, and HPV vaccine. Methods. Structured questionnaires were administered to a cross section of 737 women randomly selected from the general population in two southwestern States of Nigeria. Statistical analysis was done using SPSS computer software version 16. A P value >0.05 was considered statistically significant. Results. One hundred and seventy-six (23.9% of the respondents had knowledge of HPV; 474 (64.3% are aware of cervical cancer but only 136 (18.5% know that HPV causes cervical cancer. 200 (27.1% are aware that there is an HPV vaccine while 300 (40.7% had knowledge of Pap smear test. Two hundred and sixty (35.3% of the respondents know that early detection of HPV can prevent cervical cancer and in spite of this, only 110 (14.9% have taken the Pap smear test before while 151 (20.5% are not willing to go for the test at all. Conclusions. There is therefore the need to create proper awareness on the HPV and its possible consequence of cervical carcinoma.

  10. Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs.

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    Peruzzi, Daniela; Mesiti, Giuseppe; Ciliberto, Gennaro; La Monica, Nicola; Aurisicchio, Luigi

    2010-02-03

    Pet dogs represent a valuable pre-clinical model to assess the efficacy of oncology drugs. Additionally, canine cancers occur with an incidence similar to that of humans and share many features with human malignancies including histological appearance, tumor genetics, biological behavior and response to conventional therapies. The telomerase reverse transcriptase (TERT) is reactivated in most of human and dog tumors. Similarly, HER-2/neu oncoprotein is overexpressed in a proportion of canine breast cancers. Therefore, TERT and HER-2/neu can constitute valid tumor associated antigens (TAA), suitable targets for translational cancer immunotherapy in dogs. In this study, we have evaluated the ability of DNA electroporation (DNA-EP) and Adenovirus serotype 6 (Ad6) to induce immune responses against dog TERT (dTERT) and HER-2/neu in healthy dogs. Vaccination was effective in all treated animals and the adaptive immune response remained detectable and long-lasting in the absence of autoimmunity or other side-effects. Our results show that DNA-EP/Ad6-based cancer vaccine induces adaptive immune responses against TAA in canine subjects and support further evaluation of this approach in cancer dog patients.

  11. Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru.

    Science.gov (United States)

    Penny, Mary; Bartolini, Rosario; Mosqueira, N Rocio; LaMontagne, D Scott; Mendoza, Maria Ana; Ramos, Irma; Winkler, Jennifer L; Villafana, Jose; Janmohamed, Amynah; Jumaan, Aisha O

    2011-07-12

    Operational research using a mixed method, cross-sectional, case-study approach assessed the feasibility and health system impact of large-scale implementation of human papillomavirus (HPV) vaccination into routine vaccine delivery by the Ministry of Health in Peru. The strategy was school-based vaccination of fifth grade girls in 527 primary schools in Piura region. Our evaluation showed that school-based HPV vaccination is feasible without major changes in existing health systems. This was reflected in the opinions of health personnel, the lack of impact on other vaccine coverage, and the high HPV vaccine coverage documented in routine records and by an independent community-based survey.

  12. CIMAvax-EGF: A New Therapeutic Vaccine for Advanced Non-Small Cell Lung Cancer Patients

    Science.gov (United States)

    Saavedra, Danay; Crombet, Tania

    2017-01-01

    Lung cancer is the common fatal illness with the highest incidence and mortality globally. Epidermal growth factor receptor overexpression by tumor cells is associated with uncontrolled proliferation, angiogenesis, anti-apoptotic signals, metastization, and invasiveness. CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and Montanide ISA 51, as adjuvant. The vaccine is projected to induce antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF demonstrated to be safe and immunogenic in advanced non-small cell lung cancer (NSCLC) patients. The efficacy study was an open-label, multicentric Phase III clinical trial, which enrolled 405 advanced NSCLC patients. Patients with proven stage IIIB/IV NSCLC, who had completed four to six cycles of chemotherapy (CTP) were randomized to receive CIMAvax-EGF or best supportive care. CIMAvax-EGF resulted in a significantly larger overall survival in patients receiving at least four doses. High EGF concentration at baseline was a good predictive biomarker of the vaccine activity and a poor prognostic biomarker for the non-treated population. The proportion of CD8+CD28− cells, CD4 cells, and the CD4/CD8 ratio after first-line CTP was also associated with CIMAvax-EGF clinical benefit. After completing the Phase III, a Phase IV trial was done where the vaccine was administered in primary care units. Administering the vaccine at primary care institutions granted better access and treatment compliance. Safety was confirmed. Several clinical trials are currently ongoing to validate EGF as a predictive biomarker of CIMAvax-EGF efficacy.

  13. Specific Dioscorea Phytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines

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    Wei-Ting Chang

    2013-01-01

    Full Text Available Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC- based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL- loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h + LPS (22 h showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53% of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.

  14. Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

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    Ortendahl Jesse

    2007-10-01

    Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter

  15. Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines.

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    Yagui-Beltrán, Adam; Coussens, Lisa M; Jablons, David M

    2009-01-01

    Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumor-associated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

  16. Human papilloma viruses and cancer in the post-vaccine era.

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    Galani, E; Christodoulou, C

    2009-11-01

    Human papilloma viruses (HPV) are strong human carcinogens, in fact today they are considered as the second most frequent carcinogen. In the middle of the 1970s the hypothesis that cervical cancer may arise from viruses was established and in the 1990s the relationship between HPV and cervical neoplasia was confirmed. HPV infections are the most common sexually transmitted infections. Specific subtypes of human papilomaviruses are now considered as the etiological agents in nearly all cases of cervical cancer and cervical epithelial neoplasia. Approximately 470,000 new cases and 23,000 deaths of cervical cancer occur each year, with the majority taking place in developing countries. Cervical cancer remains among the three leading causes of cancer deaths among women below the age of 45. Human papilomaviruses are classified into two groups: high-risk (oncogenic) types and low risk types. HPV types 16, 18, 45 and 31 are considered to be the most important oncogenic types. Subtypes 16 and 18 are the causative agents of more than 50% of cervical pre-cancerous lesions, and more than 70% of cervical cancer cases. High risk subtypes are also implicated with anal, perianal and oropharyngeal carcinomas. Recently, the prophylactic bivalent HPV 16/18 and the quadrivalent HPV 6/11/16/18/ vaccines have been approved. The development of prophylactic vaccines against human papilomavirus has been hailed as one of the most significant advances of recent years and it is expected to reduce dramatically the mortality of human papilomavirus associated cancers, but has also given rise to some of the most intense scientific debates.

  17. Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population.

    Science.gov (United States)

    Paynter, Christopher A; Van Treeck, Benjamin J; Verdenius, Inge; Lau, Agnes W Y; Dhawan, Twinkle; Lash, Kayla A; Bergamini, Elizabeth A; Ekekezie, Chiazotam N; Hilal, Amna M; James, Kristen N; Alongi, Sadie; Harper, Sean M; Bonham, Aaron J; Baumgartner, Kathy B; Baumgartner, Richard N; Harper, Diane M

    2015-01-01

    Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14-26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.

  18. Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population

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    Christopher A. Paynter

    2015-01-01

    Full Text Available Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14–26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00. Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35. Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.

  19. HPV vaccination and allocative efficiency: regional analysis of the costs and benefits with the bivalent AS04-adjuvanted vaccine, from the perspective of public health, for the prevention of cervical cancer and its pre-cancerous lesions

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    Paolo Bonanni

    2012-11-01

    Full Text Available Introduction: by means of the decisions on whether to introduce the HPV vaccination, Public Health has already established the importance of associating the vaccination strategy to the policy of secondary prevention. The screening + vaccination strategy is more effective than the two methods taken individually. In support of this combined strategy and in order to make available per each region concrete elements for their regional planning, an assessment has been made, which also takes into account the effect of cross-protection regarding high-risk strains not contained in both vaccines, bivalent and quadrivalent, and more frequently responsible for pre-cancerous lesions and cervical cancer (CCU. This analysis evaluates the costs and benefits of screening + vaccination strategy in a 12-year-old female cohort. Furthermore, the paper provides results that may be useful to assess the opportunity to extend the vaccination to a second cohort of 24-25-year-old women. The analysis is preceded by a brief summary of CCU epidemiology available data, public health policies that give precise guidelines for vaccination strategies and analytical tools suitable to support public policy makers to efficiently allocate resources. Methods: two different models were used for two regional analyses.The vaccines may have different sustained- and cross-protection levels against non-vaccine oncogenic HPV-types. In the first analysis, a prevalence-based model estimated the potential net difference in HPV-related lesions (abnormal pap smear, cervical intraepithelial neoplasia (CIN, cervical cancer (CC and genital warts (GW and associated costs generated by the two vaccines. Vaccine efficacy rates were based on published data for each vaccine. Lifetime vaccine efficacy was assumed. Results are reported over one year after reaching a steady state. Incidence and treatment costs were obtained from Italian and European sources. We also performed a cost-effectiveness analysis

  20. Human papillomavirus infection, vaccination, and cervical cancer communication: the protection dilemma faced by women in southern Appalachia.

    Science.gov (United States)

    Hutson, Sadie P; Dorgan, Kelly A; Duvall, Kathryn L; Garrett, Linda H

    2011-11-30

    Human papillomavirus is the most frequently occurring sexually transmitted infection and has been recognized as the necessary cause of cervical cancer. Understanding the shift in public awareness caused by recent changes to cervical prevention is critical to addressing cervical cancer disparities in Appalachia. Since the human papillomavirus vaccine was approved for prevention, little data have been collected regarding human papillomavirus risk assessment and vaccine perceptions among Appalachian women. The purpose of the authors in this study was to investigate communication and cultural issues via a social scripting framework that could influence human papillomavirus vaccine uptake among southern Appalachian women; and explore participants' perceptions of human papillomavirus, cervical cancer, and the vaccine. A qualitative, descriptive design was employed to examine these issues in eight counties in northeast Tennessee and southwest Virginia. Thirty-nine women aged 18-49 years participated in a single individual interview or focus group session from October 2007 through August 2008. Interview and focus group data were audio-taped and transcribed verbatim. Two major themes emerged from the data: the human papillomavirus vaccine protection dilemma and spheres of silence surrounding the human papillomavirus vaccine protection dilemma. Study findings suggested areas for future research and may assist healthcare professionals in approaching southern Appalachian women as they make decisions regarding cervical cancer prevention.

  1. Sipuleucel-T: a therapeutic cancer vaccine for the treatment of castration- or hormone-refractory prostate cancer.

    Science.gov (United States)

    Bulloch, Marilyn N; Elayan, Mohammed M; Renfroe, Holly R

    2011-11-01

    Sipuleucel-T is a therapeutic cancer vaccine approved for the treatment of castration- or hormone-refractory prostate cancer. Through a novel process, it activates the body's own antigen-presenting cells to induce an immune response to prostatic acid phosphatase, a protein found on prostate cancer cells. A treatment course consists of three total infusions spread 2 weeks apart. Throughout all phases of clinical trials, sipuleucel-T has been shown to be safe and well tolerated. Sipuleucel-T has demonstrated an ability to increase overall survival by approximately 4 months when compared with placebo. However, sipuleucel-T has not shown any improvement in affecting patients' time to disease progression.

  2. 肺癌免疫逃逸机制与肺癌疫苗%The Immune Escape Mechanisms of Lung Cancer and Lung Cancer Vaccine

    Institute of Scientific and Technical Information of China (English)

    李自青; 刘宏

    2011-01-01

    Abstract: Lung cancer is a kind of disease which is seriously imperiling human health and life. The main pathogenesis of lung cancer is the occurrence of immune escape of cancer cell, which by changing surface antigens, abnormally expressing MHC-I molecules and the costimulatory molecules, highly expressing the FasL and dendritic cell function defects. Lung cancer vaccine is biological agents designed for antagonizing immune escape mechanisms of lung cancer. At present, lung cancer vaccines being developed are mainly composed of synthetic peptide vaccine, dendritic cell vaccines, genetically modified vaccines and nucleic acid vaccine, et al. Clinical trials have shown that these vaccines can stimulate active immune response for lung cancer-specific antigens, but the clinical efficacy remains to be further observed.%肺癌是严重威胁人类健康和生命的疾病.肺癌的主要发病机制是癌细胞通过表面抗原的改变、MHC-I分子和共刺激分子表达异常、树突状细胞功能缺陷以及肺癌细胞高表达FasL等机制实现了免疫逃逸.肺癌疫苗是针对肺癌免疫逃逸机制而设计的生物制剂.目前正在研制的肺癌疫苗主要有合成肽疫苗、树突状细胞疫苗、转基因疫苗和核酸疫苗等几类.临床试验表明,这些疫苗能激发针对肺癌特异性抗原的主动免疫反应,但临床效果仍有待进一步的观察.

  3. Cancer Vaccines: State of the Art of the Computational Modeling Approaches

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    Francesco Pappalardo

    2013-01-01

    Full Text Available Cancer vaccines are a real application of the extensive knowledge of immunology to the field of oncology. Tumors are dynamic complex systems in which several entities, events, and conditions interact among them resulting in growth, invasion, and metastases. The immune system includes many cells and molecules that cooperatively act to protect the host organism from foreign agents. Interactions between the immune system and the tumor mass include a huge number of biological factors. Testing of some cancer vaccine features, such as the best conditions for vaccine administration or the identification of candidate antigenic stimuli, can be very difficult or even impossible only through experiments with biological models simply because a high number of variables need to be considered at the same time. This is where computational models, and, to this extent, immunoinformatics, can prove handy as they have shown to be able to reproduce enough biological complexity to be of use in suggesting new experiments. Indeed, computational models can be used in addition to biological models. We now experience that biologists and medical doctors are progressively convinced that modeling can be of great help in understanding experimental results and planning new experiments. This will boost this research in the future.

  4. Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

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    Renee Vermeij

    2010-01-01

    Full Text Available The prognosis of epithelial ovarian cancer (EOC, the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%, 173 (68.9%, 208 (90.0%, 129 (56.3%, and 27 (11.0% of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (overexpressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (overexpression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.

  5. Knowledge, Awareness and Attitude on HPV, HPV Vaccine and Cervical Cancer among the College Students in India

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    Rashid, Shazia; Labani, Satyanarayana; Das, Bhudev C.

    2016-01-01

    Background Infection of specific high risk Human papillomaviruses (HPVs) is known to cause cervical cancer and two prophylactic vaccines have been developed against two major high risk HPV types 16 and 18 for prevention of cervical cancer. Because of societal, religious and ethical issues associated with the vaccination of adolescent girls in India together with lack of awareness about HPV and HPV vaccines, no successful HPV immunization program has been employed in India. Objective To determine knowledge, awareness and attitude of college students on HPV, HPV vaccine and cervical cancer. Method A questionnaire-based survey was conducted in a total of 1580 undergraduate students between the age group 16–26 years comprising 684 girls and 876 boys. Results Out of a total of 1580 students, girls had more knowledge about cervical cancer (82.45%, p<0.001), HPV (45.61%, p<0.001) and HPV vaccines (44%, p<0.001) when compared to those in boys. However, knowledge about the types of HPV and vaccines was poor. Interestingly, students from biology-major had more knowledge and awareness about cervical cancer (81.89%, p<0.001) and HPV (46.58%, <0.001) when compared to non-biology students. Girls from both biology and non-biology group had higher awareness compared to boys. Analysis of odds ratio (ORs) along with 95% CI showed older girls with 1.2 to 3 fold (p<0.05) higher knowledge than boys. All students agreed that girls should get vaccinated against HPV (p<0.001). Conclusion It is suggested that there is a need for educational intervention and awareness campaigns to augment HPV immunization program for control of cervical cancer in India. PMID:27861611

  6. A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.

    Science.gov (United States)

    Ebert, Lisa M; MacRaild, Sarah E; Zanker, Damien; Davis, Ian D; Cebon, Jonathan; Chen, Weisan

    2012-01-01

    Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.

  7. The future of cancer research: prevention, screening, vaccines, and tumor-specific drug combos.

    Science.gov (United States)

    Blanck, George

    2014-01-01

    New cancer research strategies have developed very rapidly over the past five years, including extensive DNA sequencing of tumor and normal cells; use of highly sensitive cancer cell detection methods; vaccine development and tumor-specific (designer) drugs. These developments have raised questions about where to concentrate efforts in the near future when establishing clinical trials, particularly important in an age of diminishing resources and during a period when competing strategies for cancer control are likely to overwhelm the opportunities for establishing large, effective clinical trials. In particular, it behooves the research community to be mindful of the inevitable, challenging obligation to responsibly choose between clinical trials that offer the credible hope of incremental advances vs. trials that are less traditional but may have revolutionary outcomes.

  8. Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

    Directory of Open Access Journals (Sweden)

    Tania Løve Aaes

    2016-04-01

    Full Text Available Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.

  9. Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology.

    Science.gov (United States)

    Laheru, Dan A; Pardoll, Drew M; Jaffee, Elizabeth M

    2005-11-01

    Recent advances in our understanding of the complex signaling pathways involved in immune system regulation, along with analyses of genetic differences between tumors and their normal cellular counterparts, have accelerated development of immune-based strategies for cancer treatment and prevention. More clinically relevant animal models have shown that successful immune-based strategies will require the integration of interventions that target specific tumor antigens with regulators of the antitumor immune response. Immunotherapy for cancer is at a critical crossroad, as therapeutics designed to target cancer-associated antigens and regulatory signaling molecules enter clinical trials. We outline here a paradigm for early-stage clinical development of immunotherapy combinations that use vaccines to drive tumor antigen-specific responses while simultaneously targeting immune regulatory pathways.

  10. Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity.

    Science.gov (United States)

    Aaes, Tania Løve; Kaczmarek, Agnieszka; Delvaeye, Tinneke; De Craene, Bram; De Koker, Stefaan; Heyndrickx, Liesbeth; Delrue, Iris; Taminau, Joachim; Wiernicki, Bartosz; De Groote, Philippe; Garg, Abhishek D; Leybaert, Luc; Grooten, Johan; Bertrand, Mathieu J M; Agostinis, Patrizia; Berx, Geert; Declercq, Wim; Vandenabeele, Peter; Krysko, Dmitri V

    2016-04-12

    Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.

  11. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer. Addendum

    Science.gov (United States)

    2009-07-01

    Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer PRINCIPAL INVESTIGATOR: Donald W. Kufe, M.D...COVERED 1 Jul 2008 – 30 Jun 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the...David Avigan, MD, Beth Israel Deaconess Medical Center, Boston, MA, in Support of Proposal, "Fusions of Breast Carcinoma and Dendritic Cells as a

  12. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer

    Science.gov (United States)

    2012-07-01

    Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer PRINCIPAL INVESTIGATOR: Donald Kufe, M.D...COVERED 1 July 2011 – 30 June 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for...have been enrolled thus far. We reported in detail the characterization of the tumor cells, the generated dendritic cells and the DC/tumor fusions

  13. Exploration of graphene oxide as an intelligent platform for cancer vaccines

    Science.gov (United States)

    Yue, Hua; Wei, Wei; Gu, Zonglin; Ni, Dezhi; Luo, Nana; Yang, Zaixing; Zhao, Lin; Garate, Jose Antonio; Zhou, Ruhong; Su, Zhiguo; Ma, Guanghui

    2015-11-01

    We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines.We explored an intelligent vaccine system via facile approaches using both experimental and theoretical techniques based on the two-dimensional graphene oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO imparted various immune activation tactics to improve the antigen immunogenicity. A high antigen adsorption was acquired, and the mechanism was revealed to be a combination of electrostatic, hydrophobic, and π-π stacking interactions. The ``folding GO'' acted as a cytokine self-producer and antigen reservoir and showed a particular autophagy, which efficiently promoted the activation of antigen presenting cells (APCs) and subsequent antigen cross-presentation. Such a ``One but All'' modality thus induced a high level of anti-tumor responses in a programmable way and resulted in efficient tumor regression in vivo. This work may shed light on the potential use of a new dimensional nano-platform in the development of high-performance cancer vaccines. Electronic

  14. Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Fan-Ping Meng; Jie Ding; Zhao-Cai Yu; Quan-Li Han; Chang-Cun Guo; Na Liu; Dai-Ming Fan

    2005-01-01

    AIM: To develop an oral attenuated Salmonella typhimurium vaccine against gastric cancer and to evaluate its efficacy in mice.METHODS: A complementary sequence of Nco I site and a sequence coding for MG7-Ag mimotope were designed at the 5' terminus of forward primer. Using p1.2 Ⅱ-HBCAg plasmid as template, PCR was performed to get a fusion gene of the mimotope and a HBcAg gene. The fusion gene was then subcloned into the plasmid pYA3341complementary to Salmonella typhimurium X4550, and the recombinant plasmid was then transformed into attenuated Salmonella typhimurium X4550. Balb/c mice were orally immunized with the recombinant Salmonella typhimurium X4550. The mice were immunized every 2 wk to reinforce the immunity. At the 6th wk, serum titer of antibody was detected by ELISA, and at the 8th wk,cellular immunity was detected by 51Cr release test. Ehrlich ascites carcinoma cells expressing MG7-Ag were used in tumor challenge assay as a model to evaluate the protective effect of the vaccine.RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than in control groups (0.9538±0.043 vs0.6531±0.018,P<0.01; 0.9538±0.043 vs0.6915±0.012, P<0.01), while in vitro 51Cr release assay of the splenocytes showed no statistical difference in the three groups. Two weeks after tumor challenge, 1 in 5 immunized mice was tumor free, while all the mice in the control group presented tumor.CONCLUSION: Oral attenuated Salmonella typhimurium vaccine against the MG7-Ag mimotope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumors in mice, and has some protective effects.

  15. Modeling flow cytometry data for cancer vaccine immune monitoring.

    Science.gov (United States)

    Frelinger, Jacob; Ottinger, Janet; Gouttefangeas, Cécile; Chan, Cliburn

    2010-09-01

    Flow cytometry (FCM) is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. In all these applications, the challenge is to detect extremely rare cell subsets while avoiding spurious positive events. To achieve this objective, it helps to be able to analyze FCM data using multiple markers simultaneously, since the additional information provided often helps to minimize the number of false positive and false negative events, hence increasing both sensitivity and specificity. However, with manual gating, at most two markers can be examined in a single dot plot, and a sequential strategy is often used. As the sequential strategy discards events that fall outside preceding gates at each stage, the effectiveness of the strategy is difficult to evaluate without laborious and painstaking back-gating. Model-based analysis is a promising computational technique that works using information from all marker dimensions simultaneously, and offers an alternative approach to flow analysis that can usefully complement manual gating in the design of optimal gating strategies. Results from model-based analysis will be illustrated with examples from FCM assays commonly used in cancer immunotherapy laboratories.

  16. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin......-layed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac® vaccine treatment in patients with progressive NSCLC....

  17. Sunitinib depletes myeloid-derived suppressor cells and synergizes with a cancer vaccine to enhance antigen-specific immune responses and tumor eradication

    NARCIS (Netherlands)

    Draghiciu, Oana; Nijman, Hans W.; Hoogeboom, Baukje Nynke; Meijerhof, Tjarko; Daemen, Toos

    2015-01-01

    The high efficacy of therapeutic cancer vaccines in preclinical studies has yet to be fully achieved in clinical trials. Tumor immune suppression is a critical factor that hampers the desired antitumor effect. Here, we analyzed the combined effect of a cancer vaccine and the receptor tyrosine kinase

  18. T-Regulatory Cells and Vaccination “Pay Attention and Do Not Neglect Them”: Lessons from HIV and Cancer Vaccine Trials

    Science.gov (United States)

    Brezar, Vedran; Godot, Véronique; Cheng, Liang; Su, Lishan; Lévy, Yves; Seddiki, Nabila

    2016-01-01

    Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit. In HIV infection, Tregs are needed during acute infection to preserve tissue integrity from an overwhelmed activation, but are not beneficial in chronic infection as they suppress anti-HIV responses. Current assays used to evaluate vaccine-induced specific responses are limited as they do not take into account antigen-specific Tregs. However, new assays, such as the OX40 assay, which allow for the simultaneous detection of a full range of Th-responses including antigen-specific Tregs responses, can overcome these issues. In this review article we will revise the role of Tregs in vaccination and review the recent work performed in the field, including the available tools to monitor them, from novel assays to humanized mouse models. PMID:27608046

  19. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    DEFF Research Database (Denmark)

    Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... in the production of the vaccine. Quantitative PCR was used to assay 74 tumor antigen genes in patients with squamous cell carcinoma of the esophagus. 81% (13/16) of tumors expressed more than five cancer/testis (CT) antigens. A total of 96 genes were assayed in the tumor cell clone (DDM1.7) used to make tumor cell...... lysate for vaccine preparation. Gene expression in DDM1.7 cells was compared with three normal tissues; 16 tumor antigen genes were induced more than ten-fold relative to normal tissues. Treatment with 5-aza-CdR induced expression of an additional 15 tumor antigens to a total of 31. MAGE-A protein...

  20. A GM-CSF and CD40L bystander vaccine is effective in a murine breast cancer model

    Directory of Open Access Journals (Sweden)

    Soliman H

    2015-12-01

    Full Text Available Hatem Soliman,1 Melanie Mediavilla-Varela,2 Scott J Antonia,3 1Department of Women's Oncology and Experimental Therapeutics, 2Department of Immunology, 3Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA Background: There is increasing interest in using cancer vaccines to treat breast cancer patients in the adjuvant setting to prevent recurrence in high risk situations or in combination with other immunomodulators in the advanced setting. Current peptide vaccines are limited by immunologic compatibility issues, and engineered autologous cellular vaccines are difficult to produce on a large scale. Using standardized bystander cell lines modified to secrete immune stimulating adjuvant substances can greatly enhance the ability to produce immunogenic cellular vaccines using unmodified autologous cells or allogeneic medical grade tumor cell lines as targets. We investigated the efficacy of a cellular vaccine using B78H1 bystander cell lines engineered to secrete granulocyte macrophage-colony stimulating factor and CD40 ligand (BCG in a murine model of breast cancer. Methods: Five-week-old female BALB/c mice were injected orthotopically in the mammary fat pad with 4T1 tumor cells. Treatment consisted of irradiated 4T1 ± BCG cells given subcutaneously every 4 days and was repeated three times per mouse when tumors became palpable. Tumors were measured two to three times per week for 25 days. The vaccine's activity was confirmed in a second experiment using Lewis lung carcinoma (LLC cells in C57BL/6 mice to exclude a model specific effect. Interferon-γ (IFN-γ and interleukin-2 (IL-2 enzyme-linked immunospots (ELISPOTS were performed on splenic lymphocytes incubated with 4T1 lysates along with immunohistochemistry for CD3 on tumor sections. Results: Tumor growth was significantly inhibited in the 4T1-BCG and LLC-BCG treatment groups when compared to 4T1 and LLC treatment groups. There were higher levels of IL-2 and IFN

  1. Vector prime/protein boost vaccine that overcomes defects acquired during aging and cancer

    DEFF Research Database (Denmark)

    Tang, Y.; Akbulut, H.; Maynard, J.;

    2006-01-01

    following the Ad-sig-TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase dramatically over that seen with vector alone, in young (2-mo-old) as well as old (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer. This vaccine also induces a 4-fold......We showed that the Ad-sig-TAA/ecdCD40L vaccine induces a tumor suppressive immune response to the hMUC-1 and rH2N tumor-associated self Ags (TAA) and to the Annexin A1 tumor vascular Ag, even in mice in which anergy exists to these Ags. When the TAA/ecdCD40L protein is given s.c. as a boost...... decrement of negative regulatory CD4CD25FOXP3-T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms....

  2. Synopsis of the 6th Walker's Cay Colloquium on Cancer Vaccines and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2004-06-01

    Full Text Available Abstract The 6th annual Cancer Vaccines and Immunotherapy Colloquium at Walker's Cay was held under the auspices of the Albert B. Sabin Vaccine Institute on March 10–13, 2004. The Colloquium consisted of a select group of 34 scientists representing academia, biotechnology and pharmaceutical industry. The main goal of this gathering was to promote in a peaceful and comfortable environment exchanges between basic and clinical science. The secondary benefit was to inspire novel bench to bedside ventures and at the same time provide feed back about promising and/or disappointing clinical results that could help re-frame some scientific question or guide the design of future trials. Several topics were covered that included tumor antigen discovery and validation, platforms for vaccine development, tolerance, immune suppression and tumor escape mechanisms, adoptive T cell therapy and dendritic cell-based therapies, clinical trials and assessment of response. Here we report salient points raised by speakers or by the audience during animated discussion that followed each individual presentation.

  3. Exploiting the immunogenic potential of cancer cells for improved dendritic cell vaccines

    Directory of Open Access Journals (Sweden)

    Lien eVandenberk

    2016-01-01

    Full Text Available Cancer immunotherapy is currently the hottest topic in the oncology field, owing predominantly to the discovery of immune checkpoint blockers. These promising antibodies and their attractive combinatorial features have initiated the revival of other effective immunotherapies like dendritic cell (DC vaccinations. Although DC-based immunotherapy can induce objective clinical and immunological responses in several tumor types, the immunogenic potential of this monotherapy is still considered suboptimal. Hence, focus should be directed on potentiating its immunogenicity by making step-by-step protocol innovations to obtain next-generation Th1-driving DC vaccines. We review some of the latest developments in the DC vaccination field, with a special emphasis on strategies that are applied to obtain a highly immunogenic tumor cell cargo to load and to activate the DCs. To this end, we discuss the effects of three immunogenic treatment modalities (ultraviolet light, oxidizing treatments and heat shock and five potent inducers of immunogenic cell death (radiotherapy, shikonin, high-hydrostatic pressure, oncolytic viruses and (hypericin-based photodynamic therapy on DC biology and their application in DC-based immunotherapy in preclinical as well as clinical settings.

  4. Human Papillomavirus-mediated cervical cancer awareness and Gardasil vaccination: a pilot survey among North Indian women.

    Science.gov (United States)

    Pandey, Saumya; Chandravati

    2013-10-01

    Human Papillomavirus (HPV)-mediated cervical cancer is a leading cause of morbidity and mortality in women worldwide, including Indian women. Cervical cancer control and prevention strategies are being adopted in developing nations to reduce the increasing burden of HPV infection in the vaccine era. The present study, therefore, aimed to evaluate cervical cancer awareness and knowledge of Gardasil vaccination in North Indian women. A pilot survey was conducted among 103 women of North Indian ethnicity residing in Lucknow/adjoining areas in state of Uttar Pradesh, during routine screening/clinic visits from June 2012 to December 2012. The study subjects were interviewed in either Hindi or English; subsequently the awareness of HPV-mediated cervical cancer and knowledge of Gardasil vaccination was assessed in terms of "yes", "no" and "no response". The study was approved by the Institutional Review Board. Written informed consent was taken from the participants. Overall, the response of participants (n = 103) in our single-centre survey-based pilot study was well-defined. The response regarding HPV-mediated cervical cancer awareness in terms of "yes", "no" and "no response" among the study subjects was 43.7, 44.7 and 11.6 %, respectively. Furthermore, in response to knowledge of HPV vaccine Gardasil, out of 103 subjects, 28.1 % answered "yes" while 37.9 and 34.0 % stated "no" and "no response", respectively. Our pilot survey may help in assessing knowledge of HPV-mediated cervical cancer and Gardasil vaccination awareness in women, and accordingly develop cost-effective cervical cancer control and prevention/public health counseling sessions in a clinical setting.

  5. Cancer Vaccine:promise in the 21st Century%癌症疫苗:21世纪征服癌症的希望

    Institute of Scientific and Technical Information of China (English)

    曾钢

    2001-01-01

    Cancer vaccine,the idea of utilizing the immune system to prevent and/or treat human cancers has been proposed for nearly a century.Only since the last decasde,the discovery of tumor-associated antigens has helped us to understand the molecular details of tumor-immune system interaction as well as provided new opportunities for cancer vaccine development.Cancer vaccine has seen remarked progress in both basic scientific research and clinical trials based on the discoveries of these studies.Inaddition,more and more efforts from industry are being made to the commercialization of these discoverise.Cancer vaccine,in combination with surgery,chemotherapy and rediation therapy may potentially provide effective treatment to most human cancers in the 21st century.

  6. Specific microtubule-depolymerizing agents augment efficacy of dendritic cell-based cancer vaccines

    Directory of Open Access Journals (Sweden)

    Chang Wei-Ting

    2011-06-01

    Full Text Available Abstract Background Damage-associated molecular patterns (DAMPs are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs. Specific microtubule-depolymerizing agents (MDAs such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs. Methods In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine. Results The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT. DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs. Conclusions Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine.

  7. Immune Monitoring in Cancer Vaccine Clinical Trials: Critical Issues of Functional Flow Cytometry-Based Assays

    Directory of Open Access Journals (Sweden)

    Iole Macchia

    2013-01-01

    Full Text Available The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs and tumor-associated antigens (TAAs and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometry- (FCM- based assays combining different phenotypic and functional markers have been developed in the past decade for informative and longitudinal analysis of polyfunctional T-cells. These technologies were designed to address the complexity and functional heterogeneity of cancer biology and cellular immunity and to define biomarkers predicting clinical response to anticancer treatment. So far, there is still a lack of standardization of some of these immunological tests. The aim of this review is to overview the latest technologies for immune monitoring and to highlight critical steps involved in some of the FCM-based cellular immune assays. In particular, our laboratory is focused on melanoma vaccine research and thus our main goal was the validation of a functional multiparameter test (FMT combining different functional and lineage markers to be applied in clinical trials involving patients with melanoma.

  8. Antitumor immunity by a dendritic cell vaccine encoding secondary lymphoid chemokine and tumor lysate on murine prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Lu; Qi Zhang; Chun-Min Liang; Shu-Jie Xia; Cui-Ping Zhong; Da-Wei Wang

    2008-01-01

    Aim: To investigate the antitumor immunity by a dendritic cell (DC) vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods: DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine (SLC) cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC+lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results: We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC+lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos-phate buffer solution (PBS) counterparts (P<0.01). Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4+, CD8+ T cell and CD11c+ DC within established tumor treated by SLC+lysate-DC vaccine than other DC vaccines (P<0.01). Conclusion: DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4+, CD8+ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.

  9. Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines.

    Science.gov (United States)

    Butt, A Q; Mills, K H G

    2014-09-18

    Vaccines that promote protective adaptive immune responses have been successfully developed against a range of infectious diseases, and these are normally administered prior to exposure with the relevant virus or bacteria. Adaptive immunity also plays a critical role in the control of tumors. Immunotherapeutics and vaccines that promote effector T cell responses have the potential to eliminate tumors when used in a therapeutic setting. However, the induction of protective antitumor immunity is compromised by innate immunosuppressive mechanisms and regulatory cells that often dominate the tumor microenvironment. Recent studies have shown that blocking these suppressor cells and immune checkpoints to allow induction of antitumor immunity is a successful immunotherapeutic modality for the treatment of cancer. Furthermore, stimulation of innate and consequently adaptive immune responses with concomitant inhibition of immune suppression, especially that mediated by regulatory T (Treg) cells, is emerging as a promising approach to enhance the efficacy of therapeutic vaccines against cancer. This review describes the immunosuppressive mechanisms controlling antitumor immunity and the novel strategies being employed to design effective immunotherapeutics against tumors based on inhibition of suppressor cells or blockade of immune checkpoints to allow induction of more potent effector T cell responses. This review also discusses the potential of using a combination of adjuvants with inhibition of immune checkpoint or suppressor cells for therapeutic vaccines and the translation of pre-clinical studies to the next-generation vaccines against cancer in humans.

  10. NGlycolylGM3/VSSP Vaccine in Metastatic Breast Cancer Patients: Results of Phase I/IIa Clinical Trial.

    Science.gov (United States)

    de la Torre, Ana; Hernandez, Julio; Ortiz, Ramón; Cepeda, Meylán; Perez, Kirenia; Car, Adriana; Viada, Carmen; Toledo, Darién; Guerra, Pedro Pablo; García, Elena; Arboláez, Migdacelys; Fernandez, Luis E

    2012-01-01

    Patients treated with vaccines based on NGlycolil gangliosides have showed benefit in progression free survival and overall survival. These molecules, which have been observed in breast cancer cells, are minimally or not expressed in normal human tissue and have been considered as antigen tumor-specific. For this reason they are very attractive to immunotherapy. A phase I/II clinical trial was carried out in metastatic breast cancer patients with the NGlycolylGM3/VSSP vaccine administered by subcutaneous route. Selecting the optimal biological doses of the vaccine in these patients was the principal objective based on the immunogenicity, efficacy and safety results. Six levels of doses of vaccine were studied. Treatment schedule consisted of five doses every two weeks and then monthly until reaching a fifteenth doses. Doses levels studied were 150, 300, 600, 900, 1200 and 1500 μg. Five patients in each level were included except at the 900 μg dose, in which ten patients were included. Immunogenicity was determined by levels of antibodies generated in patients after vaccination. The response criteria of evaluation in solid tumors (RECIST) was used to evaluate antitumoral effect. Safety was evaluated by Common Toxicity Criteria of Adverse Event (CTCAE). The vaccine administration was safe and immunogenic in all does levels. Most frequent adverse events related to vaccination were mild or moderate and were related to injection site reactions and "flu-like" symptoms. Vaccination induced specific anti-NeuGcGM3 IgM and IgG antibodies responses in all patients. Disease control (objective response or stable disease) was obtained in 72.7% of evaluated patients. Median overall survival was 15.9 months. Two patients of two different dose levels achieved overall survival values of about six years. The dose of 900 μg was selected as biological optimal dose in which overall survival was 28.5 months.

  11. 肿瘤疫苗研发进展%Progress in the Research and Development of Cancer Vaccines

    Institute of Scientific and Technical Information of China (English)

    李扬; 王敏; 孙晓北; 郭柯磊; 池慧

    2013-01-01

    In this paper, we analyzed cancer vaccine targets, R&D status and patents based on literatures re⁃trieved from Thomson Reuters Pharma Database, Integrity Database and Derwent Innovation Index Database. To keep up with global R&D priorities in cancer vaccines so as to provide background information for R&D of can⁃cer vaccine in China.%  通过检索 Thomson Reuters Pharma 数据库、Integrity 数据库和 Derwent Innovation Index 数据库,对肿瘤疫苗的研发技术靶点、研发状态、有关专利进行分析,把握国际肿瘤疫苗的技术研发重点领,为我国肿瘤疫苗研发发展提供信息据。

  12. NIH study finds two doses of HPV vaccine may be as protective as full course | Division of Cancer Prevention

    Science.gov (United States)

    Two doses of the human papillomavirus (HPV) vaccine Cervarix were as effective as the current standard three-dose regimen after four years of follow-up, according to researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues. The results of the study, based on data from a community-based clinical trial of Cervarix in Costa Rica, appeared online Sept.9, 2011, in the Journal of the National Cancer Institute. |

  13. Knowledge and attitudes about Human Papilloma Virus (HPV) vaccination and cervical cancer screening among women in rural Uganda (POSTPRINT)

    Science.gov (United States)

    2016-01-01

    about Human Papilloma Virus (HPV) vaccination and cervical cancer screening among women in rural Uganda NKONWA INNOCENT H 1,2,3* , MICHAEL J...Human Papilloma virus (HPV) strains 16 and 18. While cervical cancer is widely understood as a fatal disease, knowledge and awareness of cervical...capture assay of self – collected virginal swabs in rural Uganda for detection of human papilloma virus . J Infect Disease, 1999 1999.180; p. 1316.1319. 19

  14. Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

    Science.gov (United States)

    Hradilova, Nada; Sadilkova, Lenka; Palata, Ondrej; Mysikova, Dagmar; Mrazkova, Hana; Lischke, Robert; Spisek, Radek; Adkins, Irena

    2017-01-01

    High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4+CD25+Foxp3+ T regulatory cells and stimulated IFN-γ-producing tumor antigen-specific CD4+ and CD8+ T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8+ and CD4+ T cell responses were detected in NSCLC patient’s against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8+ T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers. PMID:28187172

  15. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  16. Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

    DEFF Research Database (Denmark)

    Toh, Han Chong; Wang, Who-Whong; Chia, Whay Kuang

    2009-01-01

    PURPOSE: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)-pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. EXPERIMENTAL DESIGN: DCs ...

  17. Optimal Finite Cancer Treatment Duration by Using Mixed Vaccine Therapy and Chemotherapy: State Dependent Riccati Equation Control

    Directory of Open Access Journals (Sweden)

    Ali Ghaffari

    2014-01-01

    Full Text Available The main objective of this paper is to propose an optimal finite duration treatment method for cancer. A mathematical model is proposed to show the interactions between healthy and cancerous cells in the human body. To extend the existing models, the effect of vaccine therapy and chemotherapy are also added to the model. The equilibrium points and the related local stability are derived and discussed. It is shown that the dynamics of the cancer model must be changed and modified for finite treatment duration. Therefore, the vaccine therapy is used to change the parameters of the system and the chemotherapy is applied for pushing the system to the domain of attraction of the healthy state. For optimal chemotherapy, an optimal control is used based on state dependent Riccati equation (SDRE. It is shown that, in spite of eliminating the treatment, the system approaches the healthy state conditions. The results show that the development of optimal vaccine-chemotherapy protocols for removing tumor cells would be an appropriate strategy in cancer treatment. Also, the present study states that a proper treatment method not only reduces the population of the cancer cells but also changes the dynamics of the cancer.

  18. Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs

    Directory of Open Access Journals (Sweden)

    Partha Basu

    2013-01-01

    Full Text Available The Human Papillomavirus (HPV vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways - it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.

  19. Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; Peng-Fen Gao; Pei-Wu Yu; Yun Rao; Li-Xin Zhou

    2006-01-01

    AIM: To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS: The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems.The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes' proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS: The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes' proliferations were remarkably increased than their parental dendritic cells.CONCLUSION: The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.

  20. Intent to participate in future cervical cancer screenings is lower when satisfaction with the decision to be vaccinated is neutral.

    Directory of Open Access Journals (Sweden)

    Natalie Marya Alexander

    Full Text Available HPV vaccination programs have adversely affected participation in future cervical cancer screening. The purpose of this study is to determine the influence of decision satisfaction with accepting/rejecting the HPV vaccine, as well as traditional clinical factors, on the intent to participate in future screening.From January 2011 through August 2012 women 18-26 years old presenting for health care in an urban college student health and wellness clinic in the US Midwest were asked to complete a descriptive and medical history survey including a six element decisional satisfaction survey scored on 5-point Likert scales, where the intent to participate in future cervical cancer screening was measured. Of the 568 women who completed the decisional satisfaction survey, 17% of those <21 years and 7% ≥ 21 years indicated no intent to participate in future cervical cancer screenings. Among women of current screening age, the univariate risk factors of race/ethnicity, contraceptive use, number of lifetime sexual partners, and receipt of HPV vaccine were not predictors of intent for future cervical cancer screening. Instead, only a history of a prior Pap test was a significant positive predictor and only a decisional satisfaction of 'neutral' (Likert score = 3 for any of the four decisional satisfaction elements was a significant negative predictor. For the decisional satisfaction element "best for me personally", there was a 78% decreased likelihood of intending to participate in future screening if the satisfaction was neutral rather than firm (aOR = 0.22, 95% CI: 0.05-0.91 and a 26 fold increased likelihood if she had had a prior Pap test (aOR = 26, 95% CI: 5-133.HPV vaccination implementation programs must help women be the owner of their decision around HPV vaccination and understand the importance of future participation in cervical cancer screening.

  1. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Science.gov (United States)

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  2. Metal based nanoparticles as cancer antigen delivery vehicles for macrophage based antitumor vaccine.

    Science.gov (United States)

    Chattopadhyay, Sourav; Dash, Sandeep Kumar; Mandal, Debasis; Das, Balaram; Tripathy, Satyajit; Dey, Aditi; Pramanik, Panchanan; Roy, Somenath

    2016-02-10

    In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.

  3. Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vincent K. Tuohy

    2016-06-01

    Full Text Available We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are “retired” from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. α-Lactalbumin is an example of a “retired” self-protein because its expression in normal tissues is confined exclusively to the breast during late pregnancy and lactation, but is also expressed in the vast majority of human triple negative breast cancers (TNBC—the most aggressive and lethal form of breast cancer and the predominant form that occurs in women at high genetic risk including those with mutated BRCA1 genes. In anticipation of upcoming clinical trials, here we provide preclinical data indicating that α-lactalbumin has the potential as a vaccine target for inducing safe and effective primary immunoprevention as well as immunotherapy against TNBC.

  4. The HPV Vaccination Crisis

    Science.gov (United States)

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  5. [Sipuleucel-T: a prostate cancer vaccine: "instructions for use" for urologists].

    Science.gov (United States)

    Ouzaid, I; Ravery, V

    2011-10-01

    Sipuleucel-T is the first approved vaccine for prostate cancer, opening the pathway for this new treatment approach. The treatment process consists in isolating the patient dentritic cells via leukapherisis, stimulate and infuse them into the patient. These enhanced cells are then able to stimulate patient T lymphocytes to target the tumour cells. The median survival in the pivotal study, IMPACT, as well as in the previously reported randomised trials, was 4.1 months longer in the sipuleucel-T group. The estimated probability of survival 36 months after randomisation was 31.7% in the sipuleucel-T group and 23.0% in the placebo group. However, the median time to objective disease progression was similar in the two groups (hazard ratio: 0.95; 95% CI, 0.77 to 1.17; P=0.63). We report herein, the treatment modalities, side effects and results in the light of recently published randomised trials.

  6. What happened to the Provenge (Sipuleucel-T) vaccine for hormone refractory prostate cancer?

    Science.gov (United States)

    Moyad, Mark A

    2007-06-01

    The preliminary data appeared promising for men with hormone refractory prostate cancer (HRPC). The Food and Drug Administration advisory panel voted 13 to 4 to approve Provenge (sipuleucel-T) and the same panel voted 17 to 0 that it was safe. However, several weeks later the vaccine was not approved. Why did this happen? Why wasn't this novel therapy at least given "provisional" approval status, which simply allows dying patients to receive the medication until the results of the next phase III trial are known? Patients need more options for HRPC because some of the most popular current choices for HRPC were never even FDA approved, but it seems clinicians and patients are desperate for more choices so they are willing to attempt almost any intervention to improve the quality and quantity of life. Regardless, the situation with Provenge is disappointing and should be re-evaluated.

  7. Preventive vaccines for cervical cancer Vacunas para prevenir el cáncer cervical

    Directory of Open Access Journals (Sweden)

    COSETTE M WHEELER

    1997-07-01

    Full Text Available The potential use of vaccines for the human papillomavirus (HPV in the prevention and treatment of cervical cancer is a possibility in the near future. Close to 20 genotypes of HPV, of the 75 that have been identified, infect the femine genital tract, but four subtypes (16, 18, 31 and 45 have been associated in close to 80% of cervical cancers. this article proposes that in order to design an effective prophylactic vaccine against HPV infection, an adequate immune response should be guaranteed through four goals; a activation of antigens present in the cell; b overcoming the host response and viral genetic variability in the T cell response; c generation of high levels of T and B memory cells; and d persistence of antigens.El potencial uso de vacunas de virus del papiloma humano (VPH en la prevención y tratamiento del cáncer cervical posiblemente será implementado durante los próximos años. Cerca de los 20 genotipos de VPH de los 75 que se encuentran identificados infectan el tracto genital femenino, pero son cuatro subtipos: 16, 18, 31 y 45 los que se han asociado en cerca de 80% a cáncer cervical. En este ensayo se plantea que para poder diseñar una vacuna profiláctica contra la infección de VPH, efectiva, se debe garantizar una adecuada respuesta inmune a través de cuatro metas: a activación de antígenos presentes en la célula; b superar la respuesta del huésped y la variabilidad genética viral en la respuesta de células T; c generación de altos niveles de células T y B de memoria, y d persistencia de antígenos.

  8. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  9. PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine

    DEFF Research Database (Denmark)

    Munir Ahmad, Shamaila; Martinenaite, Evelina; Hansen, Morten;

    2016-01-01

    We recently described naturally occurring PD-L1-specific T cells that recognize PD-L1-expressing immune cells as well as malignant cells. In the present study, we investigated whether the immunogenicity of a dendritic cell (DC)-based vaccine could be influenced by co-stimulation with a known PD-L1......-derived epitope. We incubated a PD-L1-derived peptide epitope (19 amino acids long) or a control peptide (an irrelevant HIV epitope) with peripheral blood mononuclear cells from patients with malignant melanoma who had received a DC-based vaccine. We observed a significantly higher number of T cells...... and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents....

  10. Comparison of accelerated and rapid schedules for monovalent hepatitis B and combined hepatitis A/B vaccines in children with cancer.

    Science.gov (United States)

    Köksal, Yavuz; Varan, Ali; Aydin, G Burca; Sari, Neriman; Yazici, Nalan; Yalcin, Bilgehan; Kutluk, Tezer; Akyuz, Canan; Büyükpamukçu, Münevver

    2007-12-01

    The aim of this study was to determine the efficacy of immunization against hepatitis A and B infections with "rapid" or "accelerated" schedules in children with cancer receiving chemotherapy. Fifty-one children were recruited to receive either vaccination schedule, in the "rapid vaccination schedule"; hepatitis B (group I) or combined hepatitis A/B vaccines (group III) were administered at months 0, 1, 2, and 12; in the "accelerated vaccination schedule," hepatitis B (group II) or combined hepatitis A/B (group IV) vaccines were administered on days 0, 7, 21, and 365 intramuscularly. The seroconversion rates at months 1 and 3 were 35.7 and 57.1% in group I and 25 and 18.8% in group II, respectively. Group I developed higher seroconversion rates at month 3. In group III the seroconversion rates for hepatitis B at months 1 and 3 were 54.5 and 60% and in group IV 50 and 70%, respectively. For hepatitis A, the seroconversion rates at months 1 and 3 were 81.8 and 90% in group III and 80 and 88.9% in group IV, respectively. The accelerated vaccination schedule seems to have no advantage in children receiving cancer chemotherapy except for high antibody levels at month 1. In conclusion, the accelerated vaccination schedules are not good choices for cancer patients. The combined hepatitis A/B vaccine is more effective than monovalent vaccine in cancer patients, which probably can be explained by an adjuvant effect of the antigens. The seroconversion of hepatitis A by the combined hepatitis A/B vaccination is very good in cancer patients.

  11. Sipuleucel-T: APC 8015, APC-8015, prostate cancer vaccine--Dendreon.

    Science.gov (United States)

    2006-01-01

    Sipuleucel-T [APC 8015, Provenge] is an autologous, dendritic cell-based vaccine under development with Dendreon Corporation for the treatment of androgen-independent and androgen-dependent prostate cancer. It was generated using the company's active immunotherapy platform to stimulate a patient's own immune system to specifically target and destroy cancer cells, while leaving healthy cells unharmed. This approach could provide patients with a meaningful survival benefit and an improved tolerability profile over existing anticancer therapies. Sipuleucel-T selectively targets the prostate-specific antigen (PSA) known as prostatic acid phosphatase (PAP) that is expressed in approximately 95% of prostate cancers. It is produced by ex vivo exposure of dendritic cell precursors to PA 2024, a recombinant fusion protein composed of the PAP target fused to granulocyte-macrophage colony-stimulating factor (GM-CSF) and incorporated into Dendreon's proprietary Antigen Delivery Cassette. Patients are typically administered three intravenous (IV)-infusions of the vaccine over a 1-month period as a complete course of therapy. It is undergoing late-stage clinical evaluation among patients with early and advanced prostate cancer. In November 2003, Kirin Brewery returned to Dendreon the full rights to Sipuleucel-T for Asia. In exchange, Dendreon licensed patent rights relating to the use of certain HLA-DR antibodies to Kirin for $US20 million. This amended agreement enables Dendreon to complete ongoing discussions for a worldwide marketing and sales partnership for Sipuleucel-T. Similarly, Kirin is able to develop its HLA-DR monoclonal antibodies free of potential infringement claims arising from Dendreon's patent rights to HLA-DR. The licensing agreement relates to patent rights owned by Dendreon relating to monoclonal antibodies against the HLA-DR antigen. In addition, Dendreon retains rights to develop and commercialise its two existing HLA-DR monoclonal antibodies, DN 1921 and

  12. Preventing cervical cancer in the United States: barriers and resolutions for HPV vaccination

    Directory of Open Access Journals (Sweden)

    Anna Louise Beavis

    2016-02-01

    Full Text Available HPV vaccination rates for preadolescent and adolescent girls in the United States are far behind those of other developed nations. These rates differ substantially by region and state, socioeconomic status, and insurance status. In parents and young women, a lack of awareness and a misperception of the risk of this vaccine drive low vaccination rates. In physicians, lack of comfort with discussion of sexuality, and the perception that the vaccine should be delayed to a later age contribute to low vaccination rates. Patient and physician-targeted educational campaigns, systems-based interventions, and school-based vaccine clinics offer a variety of ways to address the barriers to HPV vaccination. A diverse and culturally appropriate approach to promoting vaccine uptake has the potential to significantly improve vaccination rates in order to reach the Healthy People 2020 goal of over 80% vaccination in adolescent girls. This article reviews the disparities in HPV vaccination rates in girls in the United States, the influences of patients’, physicians’ and parents’ attitudes on vaccine uptake, and the proposed interventions that may help the US reach its goal for vaccine coverage.

  13. Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms.

    Science.gov (United States)

    Junco, Jesús A; Basalto, Roberto; Fuentes, Franklin; Bover, Eddy; Reyes, Osvaldo; Pimentel, Eulogio; Calzada, Lesvia; Castro, Maria D; Arteaga, Niurka; López, Yovisleidis; Hernández, Héctor; Bringas, Ricardo; Garay, Hilda; Peschke, Peter; Bertot, José; Guillén, Gerardo

    2008-01-01

    Prostate growth, development, functions, and neoplastic transformation is androgen dependent. Estrogens have similar effects in the ovary and breast. Previous studies using gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate (PC) and breast cancer (BC). We have synthesized a peptide mutated at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence in the same synthesis process. After repeated pig immunizations, we have demonstrated a vaccine that significantly decreased testes size (p < 0.001), prostate (p < 0.01), seminal vesicles (p < 0.01), and testosterone (T) castration [0.05 nM ml(-1) (p < 0. 01)]. Similar results were obtained in adult male and female healthy dogs and Macaca fascicularis models. These data indicate that this GnRHm1-TT vaccine is safe and able to induce significant tumor growth inhibition in the Dunning R3327-H rat androgen responsive prostate tumor model. In these rats, the immunization induced high anti-GnRH titers concomitant with T castration reduction (p < 0.01) in 90% of the animals tested. In addition, 70% of the responders exhibited tumor growth inhibition (p = 0.02) and a survival rate approximately three times longer that those of untreated rats. These data indicate that GnRHm1-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers.

  14. [State of the art about new therapeutic vaccines in prostate cancer: dendritic cells, engineered tumor cells and recombinant virus].

    Science.gov (United States)

    Eymard, Jean-Christophe; Gervais, Alban; Jarcau, Rosana; Bernard, Jacky

    2007-07-01

    Therapeutic vaccines for prostate cancer were initially reported as limited with low immunological responses and uncertain clinical benefit. Recently, new methods become available, such preparations of well-characterized autologous dendritic cells, and use of gene therapy tools to increase whole-tumor cells or host tissue immunogenicity. These are able to enhance and diversify therapeutic options. Indeed, several vaccinal approaches are being investigated, including optimized mature dendritic cells, allogeneic genetically modified tumor cells, or viral vectors. Due to the description of immunological and clinical responses, large phase III randomized trials are now conducted. After summarizing the mechanistic basis for these approaches, this review describes the experience with the most recent and promising clinical studies and introduces short-term perspectives that could lead to improvement in healthcare offer for prostate cancer patients.

  15. Human papillomavirus (HPV vaccination for the prevention of HPV 16/18 induced cervical cancer and its precursors

    Directory of Open Access Journals (Sweden)

    Greiner, Wolfgang

    2009-03-01

    Full Text Available Introduction: Essential precondition for the development of cervical cancer is a persistent human papillomavirus (HPV infection. The majority - approximately 70% - of cervical carcinomas is caused by two high-risk HPV types (16 and 18. Recently, two vaccines have been approved to the German market with the potential to induce protection against HPV 16 and HPV 18 among additional low-risk virus types. Objectives: To analyse whether HPV vaccination is effective with regard to the reduction of cervical cancer and precursors of cervical carcinoma (CIN, respectively? Does HPV vaccination represent a cost-effective alternative or supplement to present screening practice? Are there any differences concerning cost-effectiveness between the two available vaccines? Should HPV vaccination be recommended from a health economic point of view? If so, which recommendations can be conveyed with respect to a (reorganization of the German vaccination strategy? Which ethical, social and legal implications have to be considered? Methods: Based on a systematic literature review, randomized controlled trials (RCT looking at the effectiveness of HPV vaccination for the prevention of cervical carcinoma and its precursors - cervical intraepithelial neoplasia - have been identified. In addition, health economic models were identified to address the health economic research questions. Quality assessment of medical and economic literature was assured by application of general assessment standards for the systematic and critical appraisal of scientific studies. Results: Vaccine efficacy in prevention of CIN 2 or higher lesions in HPV 16 or HPV 18 negative women, who received all vaccination doses, ranges between 98% and 100%. Side effects of the vaccination are mainly associated with injection site reactions (redness, turgor, pain. No significant differences concerning serious complications between the vaccination- and the placebo-groups were reported. Results of base case

  16. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.

    Science.gov (United States)

    Kim-Schulze, Seunghee; Kim, Hong Sung; Wainstein, Alberto; Kim, Dae Won; Yang, Wein Cui; Moroziewicz, Dorota; Mong, Phyllus Y; Bereta, Michal; Taback, Bret; Wang, Qin; Kaufman, Howard L

    2008-12-01

    The gastrointestinal mucosa contains an intact immune system that protects the host from pathogens and communicates with the systemic immune system. Absorptive epithelial cells in the mucosa give rise to malignant tumors although the interaction between tumor cells and the mucosal immune system is not well defined. The pathophysiology of colorectal cancer has been elucidated through studies of hereditary syndromes, such as familial adenomatous polyposis, a cancer predisposition syndrome caused by germline mutations in the adenomatous polyposis coli tumor suppressor gene. Patients with FAP develop adenomas and inevitably progress to invasive carcinomas by the age of 40. To better delineate the role of mucosal immunity in colorectal cancer, we evaluated the efficacy of intrarectal recombinant vaccinia virus expressing the human carcinoembryonic Ag (CEA) in a murine FAP model in which mice are predisposed to colorectal cancer and also express human CEA in the gut. Mucosal vaccination reduced the incidence of spontaneous adenomas and completely prevented progression to invasive carcinoma. The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs. Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments. Thus, intrarectal vaccination induces mucosal and systemic antitumor immunity and prevents progression of spontaneous colorectal cancer. These results have implications for the prevention of colorectal cancer in high-risk individuals.

  17. Peptide Vaccination Against Cancer Testis Antigens in Combination With Azacitidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia

    DEFF Research Database (Denmark)

    Holmberg, S.; Ortved Gang, A.; Svane, I.M.;

    2016-01-01

    . The demand for more effective therapies in this patient group is huge. Though the mechanism of AZA is not fully elucidated re-expression of tumor suppressor genes can serve as a mechanism for growth arrest. In addition, there is accumulating evidence for an up-regulation of cancer testis antigens (CTA......), which could lead to increased immune recognition of tumor cells and immune-mediated tumor cell killing. CTA’s are known to be immunogenic and are only expressed at immunoprivileged sites and on malignant cells, making them attractive as targets for therapeutic cancer vaccination....

  18. Distinctive distribution of HPV genotypes in cervical cancers in multi-ethnic Suriname: implications for prevention and vaccination.

    Science.gov (United States)

    Grunberg, M G; Chan, M; Adhin, M R

    2017-01-01

    Suriname is ranked as high-risk country for cervical cancer, but recent national data of HPV prevalence and distribution in cervical cancer is scarce. In a retrospective cross-sectional study, cervical cancer incidence, HPV prevalence and HPV-type-specific distribution were investigated in all cervical cancer cases (n = 111), diagnosed in two consecutive years. HPV presence and type-specific prevalence were determined in paraffin-embedded biopsies utilizing master-nested multiplex PCR assays, targeting 14 HPV types. The age-standardized incidence rate of cervical cancer was 22·4/100 000 women, justifying revision of the current international ranking of Suriname. Eleven HPV types were detected, with the most common types in descending order of frequency: 16, 18, 45, 66, 58/52/35. HPV16 was predominant, although with markedly low presence (25%). HPV16 or 18 infections were detected in 43% of the cases, while 28% were untyped, implicating a divergent HPV-type distribution in Suriname with significant variation in the prevalence of less common high-risk virus types and/or presence of HPV16 variants. HPV-type distribution differed between ethnic groups. A vaccination efficacy of just 28-30% was anticipated, next to an uneven vaccination impact in different ethnic groups, cautioning Suriname and other multi-ethnic countries to tailor the information presented to different ethnic communities.

  19. Prevention of HPV-related cancers in Norway: cost-effectiveness of expanding the HPV vaccination program to include pre-adolescent boys.

    Directory of Open Access Journals (Sweden)

    Emily A Burger

    Full Text Available BACKGROUND: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV, causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. METHODS: A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. RESULTS: Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY gained when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered 'good value for money.' For settings with a lower cost-effectiveness threshold ($30,000/QALY, it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. CONCLUSIONS: At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is

  20. Development of an oral DNA vaccine against MG7-Ag of gastric cancer using attenuated salmonella typhimurium as carrier

    Institute of Scientific and Technical Information of China (English)

    Chang-Cun Guo; Jie Ding; Bo-Rong Pan; Zhao-Cai Yu; Quan-Li Han; Fan-Ping Meng; Na Liu; Dai-Ming Fan

    2003-01-01

    AIM: To develop an oral DNA vaccine against gastric cancer and evaluate its efficacy in mice.METHODS: The genes of the MG7-Ag mimotope and a universal Th epitope (Pan-DR epitope, PADRE) were included in the PCR primers. By PCR, the fusion gene of the two epitopes was amplified. The fusion gene was confirmed by sequencing and was then cloned into pcDNA3.1(+) plasmid. The pcDNA3.1 (+)-MG7/PADRE was used to transfect an attenuated Salrmonella typhimuriurm.C57BL/6 mice were orally immunized with 1x108 cfu Salrmonella transfectants. Salmonella harboring the empty pcDNA3.1(+) plasmid and phosphate buffer saline (PBS)were used as negative controls. At the 6th week, serum titer of MG7-Ag specific antibody was detected by ELtSA.At the 8th week cellular immunity was detected by an unprimed proliferation test of the spleenocytes by using a [3H]-thymidine incorporation assay. Ehrlich ascites carcinoma cells expressing MG7-Ag were used as a model in tumor challenge assay to evaluate the protective effect of the vaccine.RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than that in control groups (0.841 vs 0.347, P<0.01; 0.841 vs 0.298,P<0.01), while in vitro unprimed proliferation assay of the spleenocytes showed no statistical difference between those three groups. Two weeks after tumor challenge, 2 in 7 immunized mice were tumor free, while all the mice in the control groups showed tumor formation. CONCLUSION: Oral DNA vaccine against the MG7-Ag momitope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumor in mice, and the vaccine has partially protective effects.

  1. Prevention of hepatocellular carcinoma in mice by IL-2 and B7-1genes co-transfected liver cancer cell vaccines

    Institute of Scientific and Technical Information of China (English)

    Ning-Ling Ge; Sheng-Long Ye; Ning Zheng; Rui-Xia Sun; Yin-Kun Liu; Zhao-You Tang

    2003-01-01

    AIM: To study the immunoprotective effect of liver cancer vaccine with co-transfected IL-2 and B7-1 genes on hepatocarcinogenesis in mice.METHODS: The murine liver cancer cell line Hepal-6 was transfected with IL-2 and/or B7-1 gene via recombinant adenoviral vectors and the liver cancer vaccines were prepared. C57BL/6 mice were immunized with these vaccines and challenged with the parental Hepal-6 cells afterwards.The immunoprotection was investigated and the reactive T cell line was assayed.RESULTS: The immunoprotection of the tumor vaccine was demonstrated. The effect of IL-2 and B7-1 genes cotransfected Hepal-6 liver cancer vaccine (Hep6-IL2/B7vaccine) on the onset of tumor formation was the strongest.When attacked with wild Hepal-6 cells, the median survival period of the mice immunized with Hep6-IL2/B7 vaccine was the longest (68 days, χ2=7.70-11.69, P<0.05) and the implanted tumor was the smallest (z =3.20-44.10, P<0.05).The effect of single IL-2 or B7-1 gene-transfected vaccine was next to the IL2/B7 gene co-transfected group, and the mean survival periods were 59 and 54 days, respectively.The mean survival periods of wild or enhanced green fluorescence protein gene modified vaccine immunized group were 51 and 48 days, respectively. The mice in control group all died within 38 days and the implanted tumor was the largest (z=3.20-40.21, P<0.05). The cellular immunofunction test and cytotoxicity study showed that the natural killer (NK) cell, lymphokine activated killer (LAK) cell and cytotoxic T lymphocyte (CTL) activities were significantly increased in mice immunized with the Hep6-IL2/B7 vaccine, (29.5±2.5%,65.0±2.9%, 83.1±1.5% respectively, compared with other groups, P<0.05).CONCLUSION: The Hep6-IL2/B7 liver cancer vaccines can induce the mice to produce activated and specific CTL against the parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis than single gene modified or the regular tumor vaccine. Therefore, the

  2. Therapeutic Cancer Vaccines in Prostate Cancer: The Quest for Intermediate Markers of Response

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joseph W.; Bilusic, Marijo; Heery, Christopher J.; Madan, Ravi A., E-mail: madanr@mail.nih.gov [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2012-11-21

    Despite recent advances in cancer immunotherapy, no prospectively validated intermediate biomarkers exist to predict response. These biomarkers are highly desirable given modern immunotherapy’s paradoxical pattern of clinical benefit; that is, improvement in overall survival without short-term change in progression. Immunotherapy clinical trials have evaluated biomarkers that may correlate with clinical outcomes. Many of them are performed on peripheral blood to evaluate the systemic response, such as tumor-targeted humoral and cellular immunity, and cytokine responses. Accumulating evidence suggests that immune infiltrates in tumors may suggest evidence for the therapy’s mechanism of action, and have greater potential for providing prognostic and predictive information. In addition, a non-immunologic biomarker, such as tumor growth kinetics, may explain this paradoxical pattern of clinical benefit, and predict survival in patients treated with an immunotherapy. Prospective assessment and validation of these and other intermediate markers would be required to better understand their potential clinical role.

  3. Induction of p53-Specific Immunity by a p53 Synthetic Long Peptide Vaccine in Patients Treated for Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Speetjens, Frank M.; Kuppen, PeterJ. K.; Welters, Marij. J. P.; Essahsah, Farah; van den Brink, Anne Marie E. G. Voet; Lantrua, M. Graziella Kallenberg; Valentijn, A. Rob P. M.; Oostendorp, Jaap; Fathers, Lorraine M.; Nijman, Hans W.; Drijfhout, Jan W.; van de Velde, Cornelis J. H.; Melief, Cornelis J. M.; van der Burg, Sjoerd H.

    2009-01-01

    Purpose: The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal cancer, and can serve as a target for immunotherapy. The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorecta

  4. Potential use of [gammadelta] T cell-based vaccines in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Mohd Wajid A. Khan

    2014-10-01

    Full Text Available Immunotherapy is a fast advancing methodology involving one of two approaches: 1 compounds targeting immune checkpoints, and 2 cellular immunomodulators. The latter approach is still largely experimental and features in vitro generated, live immune effector cells or antigen-presenting cells (APC. [gammadelta] T cells are known for their efficient in vitro tumor killing activities. Consequently, many laboratories worldwide are currently testing the tumor killing function of [gammadelta] T cells in clinical trials. Reported benefits are modest; however, these studies have demonstrated that large [gammadelta] T cell infusions were well tolerated. Here, we discuss the potential of using human [gammadelta] T cells not as effector cells but as a novel cellular vaccine for treatment of cancer patients. Antigen-presenting [gammadelta] T cells do not require to home to tumor tissues but, instead, need to interact with endogenous, tumor-specific [alphabeta] T cells in secondary lymphoid tissues. Newly mobilised effector [alphabeta] T cells are then thought to overcome the immune blockade by creating proinflammatory conditions fit for effector T cell homing to and killing of tumor cells. Immunotherapy may include tumor antigen-loaded [gammadelta] T cells alone or in combination with immune checkpoint inhibitors.

  5. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Andreas Draube

    Full Text Available BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17 and RCC (12. Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD amounted to a clinical benefit rate (CBR of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403 revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1 and in RCC (OR 8.4, 95% CI 1.3-53.0. Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines.

  6. In silico designing breast cancer peptide vaccine for binding to MHC class I and II: A molecular docking study.

    Science.gov (United States)

    Mahdavi, Manijeh; Moreau, Violaine

    2016-12-01

    Antigenic peptides or cancer peptide vaccines can be directly delivered to cancer patients to produce immunologic responses against cancer cells. Specifically, designed peptides can associate with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells activating anti-tumor effector mechanisms by triggering helper T cell (Th) or cytotoxic T cells (CTL). In general, high binding to MHCs approximately correlates with in vivo immunogenicity. Consequently, a molecular docking technique was run on a library of novel discontinuous peptides predicted by PEPOP from Human epidermal growth factor receptor 2 (HER2 ECD) subdomain III. This technique is expected to improve the prediction accuracy in order to identify the best MHC class I and II binder peptides. Molecular docking analysis through GOLD identified the peptide 1412 as the best MHC binder peptide to both MHC class I and II molecules used in the study. The GOLD results predicted HLA-DR4, HLA-DP2 and TCR as the most often targeted receptors by the peptide 1412. These findings, based on bioinformatics analyses, can be exploited in further experimental analyses in vaccine design and cancer therapy to find possible proper approaches providing beneficial effects.

  7. Risk messages about HPV, cervical cancer, and the HPV vaccine Gardasil: a content analysis of Canadian and U.S. national newspaper articles.

    Science.gov (United States)

    Abdelmutti, Nazek; Hoffman-Goetz, Laurie

    2009-01-01

    The human papillomavirus vaccine (Gardasil) is a significant advancement in women's health. We compared the reporting of fear-inducing messages about human papillomavirus, cervical cancer, and the human papillomavirus vaccine in Canadian and U.S. national newspapers between January 2006 and December 2007. Significant differences between countries were found in the number of articles containing fear messages about human papillomavirus, cervical cancer, and the human papillomavirus vaccine. Educational level of readability was higher than recommended for the public, and the emotional tone of the articles became progressively negative over time. Our findings suggest that public discussion of some elements of the human papillomavirus vaccine message that could cause alarm or worry for women may need to be addressed within political and cultural contexts.

  8. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

    DEFF Research Database (Denmark)

    Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra;

    2007-01-01

    PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven...... patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...

  9. Development of InCVAX as a novel in situ autologous vaccine for metastatic cancers (Conference Presentation)

    Science.gov (United States)

    Hode, Tomas; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel Siu Kit; Nordquist, Robert E.; Chen, Wei R.

    2016-03-01

    A novel method, an in situ autologous whole-cell cancer vaccine (inCVAX), is being developed by Immunophotonics, Inc., for the treatment of metastatic cancers. inCVAX combines phototherapy and immunotherapy to potentially induce a systemic anti-tumor immune response in the hosts. Immunophotonics and its academic partners have spent years conducting nonclinical research, developing CMC techniques and conducting clinical research. In 2015 the company initiated a late-stage (II/III) clinical trial in South America for advanced breast cancer patients. The process of developing the inCVAX approach from a laboratory setting into clinical trials requires significant efforts from a group of dedicated engineers, scientists, and physicians. The growth of the company and its business advances demonstrated the determination of a group of visionary investors, entrepreneurs, and business leaders. This talk will chronicle the milestones of the scientific achievement, medical progress, and business development of Immunophotonics.

  10. A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer.

    Science.gov (United States)

    Chen, Gang; Gupta, Richa; Petrik, Silvia; Laiko, Marina; Leatherman, James M; Asquith, Justin M; Daphtary, Maithili M; Garrett-Mayer, Elizabeth; Davidson, Nancy E; Hirt, Kellie; Berg, Maureen; Uram, Jennifer N; Dauses, Tianna; Fetting, John; Duus, Elizabeth M; Atay-Rosenthal, Saadet; Ye, Xiaobu; Wolff, Antonio C; Stearns, Vered; Jaffee, Elizabeth M; Emens, Leisha A

    2014-10-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination

  11. Preparation and evaluation of unimolecular pentavalent and hexavalent antigenic constructs targeting prostate and breast cancer: a synthetic route to anticancer vaccine candidates.

    Science.gov (United States)

    Ragupathi, Govind; Koide, Fusataka; Livingston, Philip O; Cho, Young Shin; Endo, Atsushi; Wan, Qian; Spassova, Maria K; Keding, Stacy J; Allen, Jennifer; Ouerfelli, Ouathek; Wilson, Rebecca M; Danishefsky, Samuel J

    2006-03-01

    Several novel, fully synthetic, carbohydrate-based antitumor vaccines have been assembled. Each construct consists of multiple cancer-related antigens displayed on a single polypeptide backbone. Recent advances in synthetic methodology have allowed for the incorporation of a complex oligosaccharide terminating in a sialic acid residue (i.e., GM2) as one of the carbohydrate antigens. Details of the vaccine synthesis as well as the results of preliminary immunological investigations are described herein.

  12. DNA vaccine encoding prostatic acid phosphatase (PAP) elicits long-term T-cell responses in patients with recurrent prostate cancer.

    Science.gov (United States)

    Becker, Jordan T; Olson, Brian M; Johnson, Laura E; Davies, James G; Dunphy, Edward J; McNeel, Douglas G

    2010-01-01

    Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer and the target of several anti-tumor vaccines in earlier clinical trials. Ultimately, the goal of anti-tumor vaccines is to elicit a sustainable immune response, able to eradicate a tumor, or at least restrain its growth. We have investigated plasmid DNA vaccines and have previously conducted a phase 1 trial in which patients with recurrent prostate cancer were vaccinated with a DNA vaccine encoding PAP. In this study, we investigated the immunologic efficacy of subsequent booster immunizations, and conducted more detailed longitudinal immune analysis, to answer several questions aimed at guiding optimal schedules of vaccine administration for future clinical trials. We report that antigen-specific cytolytic T-cell responses were amplified after immunization in 7 of 12 human leukocyte antigen-A2-expressing individuals, and that multiple immunizations seemed necessary to elicit PAP-specific interferon-gamma-secreting immune responses detectable by enzyme-linked immunosorbent spot assay. Moreover, among individuals who experienced a >/=200% increase in prostate-specific antigen doubling time, long-term PAP-specific interferon-gamma-secreting T-cell responses were detectable in 6 of 8, but in only 1 of 14 individuals without an observed change in prostate-specific antigen doubling time (P=0.001). Finally, we identified that immune responses elicited could be further amplified by subsequent booster immunizations. These results suggest that future trials using this DNA vaccine, and potentially other anti-tumor DNA vaccines, could investigate ongoing schedules of administration with periodic booster immunizations. Moreover, these results suggest that DNA vaccines targeting PAP could potentially be combined in heterologous immunization strategies with other vaccines to further augment PAP-specific T-cell immunity.

  13. 宫颈癌治疗性疫苗研究进展%Advances in the research of therapeutic vaccines against cervical cancer

    Institute of Scientific and Technical Information of China (English)

    邓玲; 刘金辉; 施桥发

    2010-01-01

    宫颈癌为妇女最常见的恶性肿瘤之一,其与人乳头瘤病毒(human papillomavirus,HPV)感染密切相关.随着对HPV及其致病机理研究的深入和免疫学的发展,利用免疫学方法治疗HPV引发的疾病显示良好的前景.目前,有关HPV治疗性疫苗的研究已取得较大进展,这些疫苗包括病毒/细菌载体疫苗、肽疫苗、蛋白疫苗、DNA疫苗、细胞疫苗等.此文就HPV治疗性疫苗的研究进展做一综述.%Cervical cancer, one of the most common cancers in women, is closely associated with human papillomavirus (HPV) infection.Along with development of immunology as well as study on HPV and its pathogenic mechanism, the treatment of HPV-related diseases by immunological methods has showed excellent prospect.Great advances in therapeutic vaccines-including viral and bacterial vector vaccines, peptide and protein vaccines, nucleic acid or DNA vaccines, and cell-based vaccines- against cervical cancer have been achieved in recent years.The progress in study on therapeutic vaccines against HPV is reviewed in this paper.

  14. A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool

    Directory of Open Access Journals (Sweden)

    Hutubessy Raymond

    2012-11-01

    Full Text Available Abstract Background The purpose, methods, data sources and assumptions behind the World Health Organization (WHO Cervical Cancer Prevention and Control Costing (C4P tool that was developed to assist low- and middle-income countries (LMICs with planning and costing their nationwide human papillomavirus (HPV vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. Methods The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers are included. Both financial (or costs to the Ministry of Health and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on, social mobilization/IEC (information, education and communication, supervision, and monitoring and evaluation (M&E. The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs to estimate the cost per dose and cost per FIG. Results Over five years (2011 to 2015, the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5 in Tanzania is estimated to be US$9.2 million (excluding vaccine costs and US$31.5 million (with vaccine assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations. This is equivalent to a

  15. Alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine: effect against breast cancer in mice.

    Directory of Open Access Journals (Sweden)

    Ze Liu

    Full Text Available Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5 than did chitosan nanoparticles (C.NPs. Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer's patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl2, which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+/CD8(+/CD25(+ when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.

  16. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jorge L. Soriano

    2011-01-01

    Full Text Available The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily, in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum, followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD was 18,43 months (12,20–24,10 months, being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  17. Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Johnsen, Hans E;

    2004-01-01

    ) loaded with a cocktail of three wild-type and three modified p53 peptides are being analysed in six HLA-A2+ patients with progressive advanced breast cancer. Vaccinations were well tolerated and no toxicity was observed. Disease stabilisation was seen in two of six patients, one patient had a transient...... the treatment. In conclusion, the strategy for p53-DC vaccination seems safe and without toxicity. Furthermore, indications of both immunologic and clinical effect were found in heavily pretreated patients with advanced breast cancer. An independent clinical effect of repeated administration of DCs and IL-2 can......Peptides derived from over-expressed p53 protein are presented by class I MHC molecules and may act as tumour-associated epitopes. Due to the diversity of p53 mutations, immunogenic peptides representing wild-type sequences are preferable as a basis for a broad-spectrum p53-targeting cancer vaccine...

  18. Elucidating the T-cell reactivity against porcine IDO and RhoC to establish the pig as an animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon;

    is a requirement for activation of CTLs. Previously, the development of therapeutic anti-cancer vaccines have largely been based on rodent models, in particular mice; however the majority of these fail to establish a therapeutic response once put into clinical trials. Pigs have the potential of serving as a model...... superior to rodents as they are more closely related to humans in terms of immunology and physiology. Here, we introduce pigs as a supplementary large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, two tumor...... antigens previously identified as important players in human cancer development and progression, were used as vaccine targets. Using peptide-MHC-I binding predictors we identified IDO-derived and RhoC-derived candidate peptides potentially binding to five different broadly distributed SLA molecules. We...

  19. Helicobacter pylori CagA: from pathogenic mechanisms to its use as an anti-cancer vaccine

    Directory of Open Access Journals (Sweden)

    Markus eStein

    2013-10-01

    Full Text Available Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue (MALT lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial-to-mesenchymal transition (EMT through the injection of CagA into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell-cell and cell-matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers.

  20. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients.

    Science.gov (United States)

    Hodi, F Stephen; Butler, Marcus; Oble, Darryl A; Seiden, Michael V; Haluska, Frank G; Kruse, Andrea; Macrae, Suzanne; Nelson, Marybeth; Canning, Christine; Lowy, Israel; Korman, Alan; Lautz, David; Russell, Sara; Jaklitsch, Michael T; Ramaiya, Nikhil; Chen, Teresa C; Neuberg, Donna; Allison, James P; Mihm, Martin C; Dranoff, Glenn

    2008-02-26

    Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory pathologies, raising the possibility that the therapeutic and toxic effects of CTLA-4 blockade might be linked. Here we show that periodic infusions of anti-CTLA-4 antibodies after vaccination with irradiated, autologous tumor cells engineered to secrete GM-CSF (GVAX) generate clinically meaningful antitumor immunity without grade 3 or 4 toxicity in a majority of metastatic melanoma patients. The application of this sequential immunotherapy to advanced ovarian carcinoma patients also revealed that tumor destruction and severe inflammatory pathology could be dissociated, although further refinements are required to increase clinical responses and to minimize toxicity in this population. The extent of therapy-induced tumor necrosis was linearly related to the natural logarithm of the ratio of intratumoral CD8(+) effector T cells to FoxP3(+) regulatory T cells (Tregs) in posttreatment biopsies. Together, these findings help clarify the immunologic and clinical effects of CTLA-4 antibody blockade in previously vaccinated patients and raise the possibility that selective targeting of antitumor Tregs may constitute a complementary strategy for combination therapy.

  1. An oral DNA vaccine against MG7—Ag of gastric cancer using attenuated Salmonella typhimurium as carrier

    Institute of Scientific and Technical Information of China (English)

    ChangCunGuo; JieDing; 等

    2002-01-01

    Aims:To develop an oral DNA vaccine against gastric cancer and evaluate its efficacy in mice.Methods:The gene of the MG7-Ag mimotope and a universal Th epitop (Pan-DR epitope,PADRE) were included in the PCR primers.By PCR,the fusion gene of the two epitopes was amplified.The fusion gene was confirmed by sequencing and then cloned into pcDNA3.1(+) plasmid.The pcDNA3.1(+)-MG7/PADRE was used to transfect an anttenuatedf Salmonella typhimurium.C57BL/6 mice were orally immunized uated Salmonella typhimurium.C57BL/6 micr were orally immunized with 1×108 cfu Salmonella transfectants.Salmonella harboring the empty pcDNA3.1(+) plasmid and phosphate buffer saline (PBS) were used as negative control.At the 6th week,serum titer of MG7-Ag specific antibody was detected by ELISA.at the 8th week cellular immunity was detected by an unprimed proliferation test of the spleenocytes by using a [3H]-thymidine incorporation assay.Ehrlich ascites carcinoma cells expressing MG7-Ag were used as a model in tumor challenge assay to evaluate the protective of the vaccine.Results:Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than control groups (0.841 vs 0.374,P<0.01;0.841 vs 0.298,P<0.01),while exvivo unprimed proliferation assay of the spleenocytes showed no statistical difference between those three groups.Two weeks after tumor challenge,2 in 7 immunized mice were tumor free,while all the mice in the control groups showed tumor formation.Conclusions:Oral DNA vaccine against the MG7-Ag mimotope of gastric cancer is immunogenic.It can induce significant humoral immunity against tumor in mice,and the vaccine has partially protective effects.

  2. A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer.

    Science.gov (United States)

    Shirahama, Takahisa; Muroya, Daisuke; Matsueda, Satoko; Yamada, Akira; Shichijo, Shigeki; Naito, Masayasu; Yamashita, Takuto; Sakamoto, Shinjiro; Okuda, Koji; Itoh, Kyogo; Sasada, Tetsuro; Yutani, Shigeru

    2017-02-11

    Since the prognosis of advanced biliary tract cancer (aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide (CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination (PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/ day for 7 days before vaccination) (PPV/CPA, n=24) or PPV alone (n=25). A maximum of four HLA-matched peptides were selected based on the pre-existing peptide-specific IgG responses, followed by subcutaneous administration. T cell responses to the vaccinated peptides in the PPV/CPA arm tended to be greater than those in the PPV alone arm. The PPV/CPA arm showed significantly better progression-free survival (median time: 6.1 vs 2.9 months; hazard ratio (HR): 0.427; P = 0.008) and overall survival (median time: 12.1 vs 5.9 months; HR: 0.376; P = 0.004), compared to the PPV alone arm. The PPV alone arm, but not the PPV/CPA arm, showed significant increase in plasma IL-6 after vaccinations, which might be associated with inhibition of antigen-specific T cell responses. These results suggested that combined treatment with low dose CPA could provide clinical benefits in aBTC patients under PPV, possibly through prevention of IL-6-mediated immune suppression. Further clinical studies would be recommended to clarify the clinical efficacy of PPV/CPA in aBTC patients. This article is protected by copyright. All rights reserved.

  3. Efficacy of HPV-16 E7 Based Vaccine in a TC-1 Tumoric Animal Model of Cervical Cancer - page 483

    Directory of Open Access Journals (Sweden)

    Maryam Fazeli

    2011-01-01

    Full Text Available Objective: The human papillomavirus as an etiological agent of cervical cancer doesnot grow adequately in tissue culture systems. The tumor cell line TC-1 continuously expressesthe E6 and E7 oncogenic proteins of HPV, and is considered a suitable tool inlaboratory investigations and vaccine researches against cervical cancer.Materials and Methods: The TC-1 cell line was grown in RPMI 1650 supplemented with10% FBS, glutamine and antibiotics, and was used for tumor development in mice. Six toseven week-old tumor bearing C57BL/6 mice were divided into 3 groups consisting of 7mice per group. The first group received pcDNA-E7, the second group received pcDNA3,and the third group received phosphate buffered saline (PBS. The treated animals weremonitored for their tumor size progression and survival. At last, the tumoric tissues fromautopsied animals were fixed and examined with Mayer's hematoxylin and eosin (H&E.All experiments were done in accordance with guidelines of the Laboratory Animal EthicalCommission of Tarbiat Modares University. Data analysis was performed using the onewayANOVA followed by Tukey's test in both experimental and control groups. A p-value<0.05 was considered significant.Results: There were significant decreases in tumor growth; there were also improvementsin survival among mice in the treated groups (p<0.041. H&E stained sections fromuntreated mice were studied independently in a blinded fashion by two observers andshowed malignant neoplasms composed of severely pleomorphic tumor cells with nuclearenlargement, high nuclear-cytoplasmic (N/C ratios, and prominent nucleoli in solid andfascicular patterns of growth. High mitotic activity with extensive necrosis was also notedin both test and control groups.Conclusion: The TC-1 lung metastatic model can be used to test the efficacy of variousE7-based therapeutic cancer vaccine strategies for cervical cancer and the prevention ofHPV-related neoplasia.

  4. First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Berinstein Neil L

    2012-08-01

    Full Text Available Abstract Background DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. Methods A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose/volume cohorts in a three immunization protocol. Results DPX-0907 was shown to be safe with injection site reactions being the most commonly reported adverse event. All breast cancer patients (3/3, most of ovarian (5/6 and one third of prostate (3/9 cancer patients exhibited detectable immune responses, resulting in a 61% immunological response rate. Immune responses were generally observed in patients with better disease control after their last prior treatment. Antigen-specific responses were detected in 73% of immune responders (44% of evaluable patients after the first vaccination. In 83% of immune responders (50% of evaluable patients, peptide-specific T cell responses were detected at ≥2 time points post vaccination with 64% of the responders (39% of evaluable patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T cell memory with the ability to secrete multiple Type 1 cytokines. Conclusions The novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data supports the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting further clinical development of the vaccine. This study underscores the importance of applying vaccines in clinical settings in which patients are more likely to be

  5. Diversity of HPV types in cancerous and pre-cancerous penile lesions of South African men: implications for future HPV vaccination strategies.

    Science.gov (United States)

    Lebelo, Ramokone L; Boulet, Gaëlle; Nkosi, Cornelius M; Bida, Mechack N; Bogers, John-Paul; Mphahlele, M Jeffrey

    2014-02-01

    This study reports the detection of HPV types from cancerous and pre-cancerous penile lesions that were diagnosed histologically. Sixty-six (22 pre-cancerous and 44 cancerous lesions) tissue biopsies, received between 2004 and 2011 by the Anatomical Pathology Department at Dr. George Mukhari Hospital were selected for this study. Total DNA was extracted and genotyped using type specific real-time quantitative polymerase chain reaction (qPCR) for 18 HPV types. Of 66 samples, only 51 were included in the analysis. Overall, HPV 11 (50.9%) and HPV 16 (49.1%) showed almost similar incidence in the study patients. In pre-cancerous lesions, HPV 11 was more frequent (80.0%), followed by HPV 31 and HPV 16 at 25.0% each and other HPV types included 35 (15.0%), 59 (15.0%), 53 (10.0%), 33 (10.0%), 18 (5.0%), 51 (5.0%), 52 (5.0%), 56 (5.0%), and 67 (5.0%). For cancerous lesions, HPV 16 was the most detected (62.9%), followed by HPV 11 (34.3%), and other HPV types included 18 (11.4%), 33 (5.7%), 39 (5.7%), 45 (5.7%), 66 (5.7%), 52 (2.9%), 58 (2.9%), 6 (2.9%), and 67 (2.9%). Several lesions demonstrated multiple HPV infections, ranging from two to six different types in one lesion. The study showed high diversity of HPV types in cancerous and pre-cancerous lesions of South African males with the most frequent being HPV types 11 and 16. The data suggest that boys could directly benefit from vaccination as they are exposed to variety of HPV types as early as 10 years of age in Africa.

  6. Human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for the prevention of cervical cancer and HPV-related diseases.

    Science.gov (United States)

    Skinner, S Rachel; Apter, Dan; De Carvalho, Newton; Harper, Diane M; Konno, Ryo; Paavonen, Jorma; Romanowski, Barbara; Roteli-Martins, Cecilia; Burlet, Nansa; Mihalyi, Attila; Struyf, Frank

    2016-01-01

    Vaccines are available against human papillomavirus (HPV), the causal agent of cervical and other cancers. Efficacy data from the HPV-16/18 AS04-adjuvanted vaccine clinical trial program were reviewed. Six randomized, controlled phase II/III trials evaluating cervical endpoints enrolled women from diverse populations and geographical locations. The program analyzed extensively the cohorts most relevant from a public health perspective: the total vaccinated cohort (TVC), approximating a general population including those with existing or previous HPV infection, and TVC-naïve, approximating a population of young women before sexual debut. Results show that the vaccine reduces HPV-16/18 infection and associated cervical endpoints in women regardless of age, location, or sexual experience. It provides cross-protection against some non-vaccine oncogenic HPV types and types causing genital warts, and may be effective against vulvar, oral, and anal HPV infection. Early epidemiology data following its introduction suggest a decline in the prevalence of vaccine and some non-vaccine HPV types.

  7. Human Papillomavirus (HPV) Vaccine (Cervarix)

    Science.gov (United States)

    ... symptoms, and go away on their own. But HPV can cause cervical cancer in women. Cervical cancer is the 2nd leading ... vaccine you are getting is one of two HPV vaccines that can be given to prevent cervical cancer. It is given to females only.The other ...

  8. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

    Directory of Open Access Journals (Sweden)

    Jin Zheng

    2012-06-01

    Full Text Available A dendritic cell (DC-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC maturation. The mean fluorescence intensity (MFI of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

  9. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jin [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Qiang [Department of Hematology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jiandong [Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Ren, Qinyou [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Cao, Wei [Department of Interventional Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, Jingyue; Yu, Zhaocai [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Yu, Fang [Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Xi' an, Shaanxi (China); Wu, Yanlan [Department of Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Shi, Hengjun [Department of Traditional Chinese and Western Medicine of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China); Liu, Wenchao [Department of Oncology, State Key Discipline of Cell Biology, Xijing Hospital, the Fourth Military Medical University, Xi' an, Shaanxi (China)

    2012-04-27

    A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

  10. The Effectiveness of a Facebook-Assisted Teaching Method on Knowledge and Attitudes about Cervical Cancer Prevention and HPV Vaccination Intention among Female Adolescent Students in Taiwan

    Science.gov (United States)

    Lai, Ching-Yi; Wu, Wei-Wen; Tsai, Shao-Yu; Cheng, Su-Fen; Lin, Kuan-Chia; Liang, Shu-Yuan

    2015-01-01

    Background: Lack of education is a known barrier to vaccination, but data on the design and effectiveness of interventions remain limited. Objective: This study aims to identify the effectiveness of a Facebook-assisted teaching method on female adolescents' knowledge and attitudes about cervical cancer prevention and on their human papillomavirus…

  11. Research progress on the therapeutic cancer vaccines and its application%治疗性肿瘤疫苗的研究及其应用进展

    Institute of Scientific and Technical Information of China (English)

    黄晨西; 高萍

    2015-01-01

    To eliminate cancer hazards to human health,the development of the therapeutic cancer vaccine has been given more and more attention.By contrast of tradition therapy,cancer immunotherapy take the advantage of being able to achieve target therapy and take modest harm to organism.Here,we first idiscussed the mechanisms of cancer immune escape,and reviewed the design principles of therapeutic cancer vaccine,as well as the latest research progress of therapeutic cancer vaccine and its application.%为了消除肿瘤对人类健康的危害,治疗性肿瘤疫苗的研发日益受到人们的重视.相对于传统治疗手段,肿瘤免疫治疗具有靶向性高、对机体伤害小的优点.本文首先对肿瘤的免疫逃脱机制进行了探讨,并对治疗性肿瘤疫苗的设计原则,以及各种治疗性肿瘤疫苗的最新研究进展以及应用进行了回顾,最后对肿瘤疫苗的发展进行了展望.

  12. Inclusion of the benefits of enhanced cross-protection against cervical cancer and prevention of genital warts in the cost-effectiveness analysis of human papillomavirus vaccination in the Netherlands

    Directory of Open Access Journals (Sweden)

    Westra Tjalke A

    2013-02-01

    Full Text Available Abstract Background Infection with HPV 16 and 18, the major causative agents of cervical cancer, can be prevented through vaccination with a bivalent or quadrivalent vaccine. Both vaccines provide cross-protection against HPV-types not included in the vaccines. In particular, the bivalent vaccine provides additional protection against HPV 31, 33, and 45 and the quadrivalent vaccine against HPV31. The quadrivalent vaccine additionally protects against low-risk HPV type 6 and 11, responsible for most cases of genital warts. In this study, we made an analytical comparison of the two vaccines in terms of cost-effectiveness including the additional benefits of cross-protection and protection against genital warts in comparison with a screening-only strategy. Methods We used a Markov model, simulating the progression from HPV infection to cervical cancer or genital warts. The model was used to estimate the difference in future costs and health effects of both HPV-vaccines separately. Results In a cohort of 100,000 women, use of the bivalent or quadrivalent vaccine (both at 50% vaccination coverage reduces the cervical cancer incidence by 221 and 207 cases, corresponding to ICERs of €17,600/QALY and €18,900/QALY, respectively. It was estimated that the quadrivalent vaccine additionally prevents 4390 cases of genital warts, reducing the ICER to €16,300/QALY. Assuming a comparable willingness to pay for cancer and genital warts prevention, the difference in ICERs could justify a slightly higher price (~7% per dose in favor of the quadrivalent vaccine. Conclusions Clearly, HPV vaccination has been implemented for the prevention of cervical cancer. From this perspective, use of the bivalent HPV vaccine appears to be most effective and cost-effective. Including the benefits of prevention against genital warts, the ICER of the quadrivalent HPV vaccine was found to be slightly more favourable. However, current decision-making on the introduction of HPV

  13. DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time.

    Science.gov (United States)

    Chudley, Lindsey; McCann, Katy; Mander, Ann; Tjelle, Torunn; Campos-Perez, Juan; Godeseth, Rosemary; Creak, Antonia; Dobbyn, James; Johnson, Bernadette; Bass, Paul; Heath, Catherine; Kerr, Paul; Mathiesen, Iacob; Dearnaley, David; Stevenson, Freda; Ottensmeier, Christian

    2012-11-01

    We report on the immunogenicity and clinical effects in a phase I/II dose escalation trial of a DNA fusion vaccine in patients with prostate cancer. The vaccine encodes a domain (DOM) from fragment C of tetanus toxin linked to an HLA-A2-binding epitope from prostate-specific membrane antigen (PSMA), PSMA(27-35). We evaluated the effect of intramuscular vaccination without or with electroporation (EP) on vaccine potency. Thirty-two HLA-A2(+) patients were vaccinated and monitored for immune and clinical responses for a follow-up period of 72 weeks. At week 24, cross-over to the immunologically more effective delivery modality was permitted; this was shown to be with EP based on early antibody data, and subsequently, 13/15 patients crossed to the +EP arm. Thirty-two HLA-A2(-) control patients were assessed for time to next treatment and overall survival. Vaccination was safe and well tolerated. The vaccine induced DOM-specific CD4(+) and PSMA(27)-specific CD8(+) T cells, which were detectable at significant levels above baseline at the end of the study (p = 0.0223 and p = 0.00248, respectively). Of 30 patients, 29 had a measurable CD4(+) T-cell response and PSMA(27)-specific CD8(+) T cells were detected in 16/30 patients, with or without EP. At week 24, before cross-over, both delivery methods led to increased CD4(+) and CD8(+) vaccine-specific T cells with a trend to a greater effect with EP. PSA doubling time increased significantly from 11.97 months pre-treatment to 16.82 months over the 72-week follow-up (p = 0.0417), with no clear differential effect of EP. The high frequency of immunological responses to DOM-PSMA(27) vaccination and the clinical effects are sufficiently promising to warrant further, randomized testing.

  14. A Feasibility Study of Cyclophosphamide, Trastuzumab, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2+ Metastatic Breast Cancer

    Science.gov (United States)

    Chen, G; Gupta, R; Petrik, S; Laiko, M; Leatherman, JM; Asquith, JM; Daphtary, MM; Garrett-Mayer, E; Davidson, NE; Hirt, K; Berg, M; Uram, JN; Dauses, T; Fetting, J; Duus, EM; Atay-Rosenthal, S; Ye, X; Wolff, AC; Stearns, V; Jaffee, EM; Emens, LA

    2014-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide (CY) augments vaccine activity in tolerant neu mice and metastatic breast cancer (MBC) patients. HER-2-specific monoclonal antibodies (MAb) enhance vaccine activity in neu mice. We hypothesized that CY-modulated vaccination with HER-2-specific MAb safely induces relevant HER-2-specific immunity in neu mice and HER-2+ MBC patients. Adding both CY and the HER-2-specific MAb 7.16.4 to vaccination maximized HER-2-specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We therefore conducted a single arm feasibility study of CY, an allogeneic HER-2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 HER-2+ MBC patients. Primary clinical trial objectives were safety and clinical benefit (CB), in which CB represents complete response+partial response+stable disease. Secondary study objectives were to assess HER-2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Subjects received three monthly vaccinations, with a boost 6-8 months from trial entry. This combination immunotherapy was safe, with CB rates at 6 months and 1 year of 55% (95% CI:32-77%, p=0.013) and 40% (95% CI:19-64%) respectively. Median progression-free survival (PFS) and overall survival (OS) were 7 (95% CI:4-16) and 42 months (95% CI:22-70) respectively. Increased HER-2-specific DTH developed in 7/20 subjects (of whom 4 had CB (95% CI:18-90)), with a trend toward longer PFS and OS in DTH responders. Polyfunctional HER-2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of CY-modulated vaccination with trastuzumab is warranted. (Clinicaltrials.gov identifier: NCT00399529) PMID:25116755

  15. Therapeutic antitumor efficacy of tumor-derived autophagosome (DRibble vaccine on head and neck cancer

    Directory of Open Access Journals (Sweden)

    Su H

    2015-03-01

    DC cross-presenting antigens on upregulated MHC-I, suggesting that DRibbles be deployed as an effective antitumor vaccine for head and neck cancer immunotherapy in clinical trials. Keywords: autophagy, nanoparticles, dendritic cells, antitumor immunity, head and neck cancer

  16. Recent advance in carbohydrate-based cancer vaccines%肿瘤糖疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    霍常鑫; 叶新山

    2012-01-01

    The abnormal glycans expressing on the surface of tumor cells are good targets to develop carbohydrate-based anti-cancer vaccines. However, one of the major problems is that carbohydrate antigens possess weak immunogenicity. This review summarizes the recent efforts to overcome this problem: glycoconjugates produced by coupling the carbohydrate antigens and proper carrier proteins improve their immunogenicity, many glycoconjugates have entered clinical trials; the vaccines become chemically well-defined when coupling the carbohydrate antigens with a T-cell peptide epitope and an immunostimulant to form fully synthetic multi-component glycoconjugate vaccines; the modification of carbohydrate antigens in combination with the technology of metabolic oligosaccharide engineering of tumor cells induces a strong immune response; and the fact that the antibodies elicited against the unnatural carbohydrate antigens can recognize the native carbohydrate antigens on tumor cells provides a new promising strategy for the development of anti-cancer vaccines.%肿瘤细胞表面异常表达的糖抗原为肿瘤糖疫苗的研究提供了合适的靶标,然而由于这些糖抗原的免疫原性较差,这又给糖疫苗的发展带来了很大的困难.本文概述了近年来科学工作者在提高肿瘤糖疫苗的免疫原性方面所做的努力:半合成的肿瘤糖疫苗将糖抗原与蛋白共价连接,已经有很多疫苗进入了临床试验;随后发展的全合成的肿瘤糖疫苗将糖抗原、T细胞表位和内源性佐剂共价连接,使疫苗的结构和组成更加确定;基于细胞代谢糖工程的肿瘤糖疫苗将非天然的糖疫苗与细胞表面代谢糖工程相结合,得到了强烈的免疫应答;某些基于天然糖抗原结构修饰的疫苗产生的抗体也可以与天然糖抗原发生交叉反应,这为肿瘤糖疫苗的发展提供了新的方向.

  17. Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial

    Directory of Open Access Journals (Sweden)

    Kim YongMan

    2011-10-01

    Full Text Available Abstract Background Ten cancer patients (Six renal cell carcinoma and four breast cancer patients were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration. Methods Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay, NK activity and the cytokine modulation were measured. Results Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses. Conclusion Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating

  18. Cross-sectional and longitudinal analysis of cancer vaccination trials registered on the US Clinical Trials Database demonstrates paucity of immunological trial endpoints and decline in registration since 2008

    Directory of Open Access Journals (Sweden)

    Lu L

    2014-09-01

    Full Text Available Liangjian Lu,1 Haixi Yan,1 Vijay Shyam-Sundar,1 Tobias Janowitz2 1School of Clinical Medicine, 2Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK Introduction: Cancer vaccination has been researched as a means of treating and preventing cancer, but successful translational efforts yielding clinical therapeutics have been limited. Numerous reasons have been offered in explanation, pertaining both to the vaccine formulation, and the clinical trial methodology used. This study aims to characterize the tumor vaccine clinical trial landscape quantitatively, and explore the possible validity of the offered explanations including the translational obstacles posed by the current common endpoints.Methods: We performed a detailed cross-sectional and longitudinal analysis of tumor vaccine trials (n=955 registered in the US Clinical Trials database.Results: The number of tumor vaccine trials initiated per annum has declined 30% since a peak in 2008. In terms of vaccine formulation, 25% of trials use tumor cell/lysate preparations; whereas, 73% of trials vaccinate subjects against defined protein/peptide antigens. Also, 68% of trials do not use vectors for antigen delivery. Both these characteristics of tumor vaccines have remained unchanged since 1996. The top five types of cancer studied are: melanoma (22.6%; cervical cancer (13.0%; breast cancer (11.3%; lung cancer (9.5%; and prostate cancer (9.4%. In addition, 86% of the trials are performed where there is established disease rather than prophylactically, of which 67% are performed exclusively in the adjuvant setting. Also, 42% of Phase II trials do not measure any survival-related endpoint, and only 23% of Phase III trials assess the immune response to vaccination.Conclusion: The clinical trial effort in tumor vaccination is declining, necessitating a greater urgency in identifying and removing the obstacles to clinical translation. These obstacles may

  19. Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination.

    Science.gov (United States)

    Jalilvand, Somayeh; Shoja, Zabihollah; Nourijelyani, Keramat; Tohidi, Hamid Reza; Hamkar, Rasool

    2015-02-01

    To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.

  20. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    Science.gov (United States)

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  1. Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine.

    Science.gov (United States)

    Ohtake, Junya; Ohkuri, Takayuki; Togashi, Yuji; Kitamura, Hidemitsu; Okuno, Kiyotaka; Nishimura, Takashi

    2014-09-01

    We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4(+) and CD8(+) T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4(+) Th1 cells and CD8(+) Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine.

  2. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

    Directory of Open Access Journals (Sweden)

    Minamida Hidetoshi

    2004-06-01

    Full Text Available Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL recognized by CD8+ cytotoxic T lymphocytes (CTLs. We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2, general malaise (grade 1, and fever (grade 1. No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9 decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.

  3. Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Asanuma Hiroko

    2008-05-01

    Full Text Available Abstract Background We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. Methods We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. Results In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1, and another had general malaise (grade 1 and fever (grade 1. Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD. Immunologically, in 3 of the 10 patients (30%, an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%, although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. Conclusion This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more

  4. In silico design of discontinuous peptides representative of B and T-cell epitopes from HER2-ECD as potential novel cancer peptide vaccines.

    Science.gov (United States)

    Manijeh, Mahdavi; Mehrnaz, Keyhanfar; Violaine, Moreau; Hassan, Mohabatkar; Abbas, Jafarian; Mohammad, Rabbani

    2013-01-01

    At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

  5. Evaluation of Prostatic Acid Phosphatase (PAP) as a Candidate Antigen for the Development of Cancer Vaccines for Prostate Cancer

    Science.gov (United States)

    2001-10-01

    colony-stimulating factor as a vaccine adjuvant elicits both a cellular and humoral response to recombinant human granu - locyte-macrophage colony...cells in recruiting CD8+ CTLs (4) and other inflammatory cells such as macrophages and eosinophils (5). CTLs have generally been believed to be the... eosinophils . Cytotoxic T lymphocytes (CTL) have long been considered to be the primary effector cell population critical for effective antitumor immunity

  6. Designing HER2 vaccines.

    Science.gov (United States)

    Foy, Teresa M; Fanger, Gary R; Hand, Susan; Gerard, Catherine; Bruck, Claudine; Cheever, Martin A

    2002-06-01

    HER2/neu is a compelling cancer vaccine candidate because it is overexpressed on some cancer cells relative to normal tissues, it is known to be immunogenic in both animal models and in humans, and it is already known to be targetable by the antibody component of the immune system in the form of monoclonal antibody therapy with trastuzumab. Vaccines offer the theoretical advantage of being able to elicit T-cell responses in addition to antibody responses. HER2 vaccines have been shown to provide benefit in animal models and to be immunogenic in humans. However, the optimal vaccine formulation is not yet known and the therapeutic efficacy of the vaccines in humans has not yet been evaluated. HER2 vaccine approaches currently being tested include peptide-based, DNA plasmid-based, and protein-based vaccines. Our group has developed and started testing a protein-based vaccine composed of both the extracellular domain of HER2 and the carboxyl terminal autophosphorylation portion of the intracellular domain. The extracellular domain was retained to provide for antibody targeting. The kinase domain of the intracellular domain was excluded because of its high degree of homology to other human kinases. The carboxyl terminal autophosphorylation domain was retained because it is the most unique and possibly most immunogenic portion of the HER2 molecule with the least homology to other members of the HER family. The vaccine, termed dHER2, is immunogenic in mice and primates. In animal models it can elicit CD8 and CD4 T-cell responses as well as antibody responses that suppress the growth of HER2-positive cancer cells in vitro and in vivo. Vaccine trials are contemplated in patients with breast cancer that will determine whether the vaccine construct is similarly immunogenic in humans.

  7. A protocol for generation of clinical grade mRNA-transfected monocyte-derived dendritic cells for cancer vaccines.

    Science.gov (United States)

    Mu, L J; Gaudernack, G; Saebøe-Larssen, S; Hammerstad, H; Tierens, A; Kvalheim, G

    2003-11-01

    With the aim of producing large quantities of mRNA-transfected monocyte-derived dendritic cells (DCs) to be used as cancer vaccines, a new clinical grade procedure has been developed. Peripheral blood mononuclear cells (PBMCs) obtained by leukapheresis were enriched for monocytes by immunomagnetic depletion of CD19+ B cells and CD2+ T cells employing the ISOLEX 300i device. After 5 days of culture of enriched monocytes in gas permeable Teflon bags, using serum-free medium supplemented with granulocyte/macrophage-colony stimulating factor and interleukin-4 (IL-4), immature DCs were generated. Following transfection with mRNA from three human prostate cancer cell lines (DU145, LNCaP and PC-3), employing a newly developed square wave electroporation procedure, the immature DCs were immediately transferred to Teflon bags and matured for 48 h, using serum-free medium supplemented with IL-1alpha, IL-6, tumour necrosis factor-alpha and PGE2. The electroporation procedure efficiently transferred mRNA into the DCs with minor effect on the viability of the cells. The generated matured transfected DCs show high expression of the antigens CD83, CD80, CD86 and human leucocyte antigen-DR. Freezing and thawing of the transfected matured DCs had minor effect on cell viability and the phenotype. From 4 x 109 PBMCs, about 1 x 108 transfected matured DCs are produced. The thawed transfected DCs were able to elicit primary T-cell responses in vitro against antigens encoded by the prostate cancer mRNA as shown by enzyme-linked immunospot assay using mock-transfected DCs as control. Based on these results, clinical trials in cancer patients have been initiated.

  8. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer Vacunas contra virus del papiloma humano y perspectivas para la prevención y el control del cáncer cervicouterino

    OpenAIRE

    Alejandro García-Carrancá

    2003-01-01

    Today, "persistent" infections by certain types of human papillomavirus (HPV) are considered necessary for developing cervical cancer. Producing efficient vaccines against these viruses may eventually lead to a great reduction in incidence and mortality rates of this cancer. In the case of HPV, the production of traditional vaccines usually based in dead or attenuated viruses is not possible due in part to the lack of systems where large quantities of viral particles could be obtained. Fortun...

  9. Juzentaihoto Failed to Augment Antigen-Specific Immunity but Prevented Deterioration of Patients’ Conditions in Advanced Pancreatic Cancer under Personalized Peptide Vaccine

    Directory of Open Access Journals (Sweden)

    Shigeru Yutani

    2013-01-01

    Full Text Available Juzentaihoto (JTT is a well-known Japanese herbal medicine, which has been reported to modulate immune responses and enhance antitumor immunity in animal models. However, it is not clear whether JTT has similar effects on humans. In particular, there is little information on the effects of JTT in antigen-specific immunity in cancer patients. Here we conducted a randomized clinical study to investigate whether combined usage of JTT could affect antigen-specific immunity and clinical findings in advanced pancreatic cancer patients undergoing personalized peptide vaccination (PPV, in which HLA-matched vaccine antigens were selected based on the preexisting host immunity. Fifty-seven patients were randomly assigned to receive PPV with (n=28 or without (n=29 JTT. Unexpectedly, JTT did not significantly affect cellular or humoral immune responses specific to the vaccine antigens, which were determined by antigen-specific interferon-γ secretion in T cells and antigen-specific IgG titers in plasma, respectively. Nevertheless, JTT prevented deterioration of patients’ conditions, such as anemia, lymphopenia, hypoalbuminemia, plasma IL-6 elevation, and reduction of performance status, which are frequently observed in advanced cancers. To our knowledge, this is the first clinical study that examined the immunological and clinical effects of JTT in cancer patients undergoing immunotherapy in humans.

  10. Group sequential monitoring based on the weighted log-rank test statistic with the Fleming-Harrington class of weights in cancer vaccine studies.

    Science.gov (United States)

    Hasegawa, Takahiro

    2016-09-01

    In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log-rank tests with the Fleming-Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming-Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long-term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log-rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study.

    Science.gov (United States)

    Barro, Ana M Bada; Rivero, Arianna Iglesias; Goñi, Avelina León; Navarro, Bárbara O González; Angarica, Meilis Mesa; Ramírez, Belinda Sánchez; Bedoya, Darel Martínez; Triana, Consuelo González; Rodríguez, Axel Mancebo; Parada, Ángel Casacó

    2012-12-17

    Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients.

  12. Cancer and Stroma-Targeted Immunotherapy with a Genetically Modified DC Vaccine

    Science.gov (United States)

    2013-05-01

    of Defense (DOD) Breast Cancer Research Program (BCRP) Era of Hope Meeting, August 2-5, 2011. Orlando Marriott World Center Hotel , Orlando, FL. 2... Marriott World Center Hotel , Orlando, FL. 2. Publication: Kakarla S, Song XT, Gottschalk S. Cancer-associated fibroblasts as targets for

  13. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2013-10-01

    tumor T cells from patients with major subtypes of breast cancer. 1. Generate reagents and identify conditions for experiments to follow: months...cancer cell line using a freeze thaw method. From 68 million cells we obtained 6.8mg of protein, as measured by a Bradford assay. Pelleting the

  14. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

    NARCIS (Netherlands)

    Van De Wall, Stephanie; Ljungberg, Karl; Peng IP, Peng; Boerma, Annemarie; Nijman, Hans W.; Liljeström, Peter; Daemen, Toos

    2014-01-01

    Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered

  15. Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

    Science.gov (United States)

    Wada, Hisashi; Isobe, Midori; Kakimi, Kazuhiro; Mizote, Yu; Eikawa, Shingo; Sato, Eiichi; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Yamasaki, Makoto; Miyata, Hiroshi; Matsushita, Hirokazu; Udono, Heiichiro; Seto, Yasuyuki; Yamada, Kazuhiro; Nishikawa, Hiroyoshi; Pan, Linda; Venhaus, Ralph; Oka, Mikio; Doki, Yuichiro; Nakayama, Eiichi

    2014-01-01

    We conducted a clinical trial of an NY-ESO-1 cancer vaccine using 4 synthetic overlapping long peptides (OLP; peptides #1, 79-108; #2, 100-129; #3, 121-150; and #4, 142-173) that include a highly immunogenic region of the NY-ESO-1 molecule. Nine patients were immunized with 0.25 mg each of three 30-mer and a 32-mer long NY-ESO-1 OLP mixed with 0.2 KE Picibanil OK-432 and 1.25 mL Montanide ISA-51. The primary endpoints of this study were safety and NY-ESO-1 immune responses. Five to 18 injections of the NY-ESO-1 OLP vaccine were well tolerated. Vaccine-related adverse events observed were fever and injection site reaction (grade 1 and 2). Two patients showed stable disease after vaccination. An NY-ESO-1-specific humoral immune response was observed in all patients and an antibody against peptide #3 (121-150) was detected firstly and strongly after vaccination. NY-ESO-1 CD4 and CD8 T-cell responses were elicited in these patients and their epitopes were identified. Using a multifunctional cytokine assay, the number of single or double cytokine-producing cells was increased in NY-ESO-1-specific CD4 and CD8 T cells after vaccination. Multiple cytokine-producing cells were observed in PD-1 (-) and PD-1 (+) CD4 T cells. In conclusion, our study indicated that the NY-ESO-1 OLP vaccine mixed with Picibanil OK-432 and Montanide ISA-51 was well tolerated and elicited NY-ESO-1-specific humoral and CD4 and CD8 T-cell responses in immunized patients.

  16. The Peru Cervical Cancer Screening Study (PERCAPS): the design and implementation of a mother/daughter screen, treat, and vaccinate program in the Peruvian jungle.

    Science.gov (United States)

    Abuelo, Carolina E; Levinson, Kimberly L; Salmeron, Jorge; Sologuren, Carlos Vallejos; Fernandez, Maria Jose Vallejos; Belinson, Jerome L

    2014-06-01

    Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100% of participants gave an HPV sample and 99.7% reported high satisfaction; 81% of HPV + women were treated, and 57% returned for 6-month followup. Vaccine intervention: 98% of girls received the 1st vaccine, 88% of those received the 2nd, and 65% the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions.

  17. Personalized peptide vaccination for advanced biliary tract cancer: IL-6, nutritional status and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis.

    Science.gov (United States)

    Yoshitomi, Munehiro; Yutani, Shigeru; Matsueda, Satoko; Ioji, Tetsuya; Komatsu, Nobukazu; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo; Sasada, Tetsuro; Kinoshita, Hisafumi

    2012-03-01

    Considering that the prognosis of patients with advanced biliary tract cancer (BTC) remains very poor, with a median survival of less than 1 year, new therapeutic approaches need to be developed. In the present study, a phase II clinical trial of personalized peptide vaccination (PPV) was conducted in advanced BTC patients to evaluate the feasibility of this treatment and to identify potential biomarkers. A maximum of 4 human leukocyte antigen-matched peptides, which were selected based on the pre-existing host immunity prior to vaccination, were subcutaneously administered (weekly for 6 consecutive weeks and bi-weekly thereafter) to 25 advanced BTC patients without severe adverse events. Humoral and/or T cell responses specific to the vaccine antigens were substantially induced in a subset of the vaccinated patients. As shown by multivariate Cox regression analysis, lower interleukin-6 (IL-6) and higher albumin levels prior to vaccination and greater numbers of selected vaccine peptides were significantly favorable factors for overall survival [hazard ratio (HR)=1.123, 95% confidence interval (CI) 1.008-1.252, P=0.035; HR=0.158, 95% CI 0.029-0.860, P=0.033; HR=0.258, 95% CI 0.098-0.682, P=0.006; respectively]. Based on the safety profile and substantial immune responses to vaccine antigens, PPV could be a promising approach for refractory BTC, although its clinical efficacy remains to be investigated in larger-scale prospective studies. The identified biomarkers are potentially useful for selecting BTC patients who would benefit from PPV.

  18. Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial

    Science.gov (United States)

    ANTONILLI, MORENA; RAHIMI, HASSAN; VISCONTI, VALERIA; NAPOLETANO, CHIARA; RUSCITO, ILARY; ZIZZARI, ILARIA GRAZIA; CAPONNETTO, SALVATORE; BARCHIESI, GIACOMO; IADAROLA, ROBERTA; PIERELLI, LUCA; RUGHETTI, AURELIA; BELLATI, FILIPPO; PANICI, PIERLUIGI BENEDETTI; NUTI, MARIANNA

    2016-01-01

    Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID:26892612

  19. Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2007-09-01

    Full Text Available Abstract Background Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC, there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC, we are currently conducting a pilot-phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. Methods NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF is given continuously (at a rate of 50 μg/24 h at the site of vaccination via minipump for six consecutive days after each vaccination. Results To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH skin

  20. HPV-vaccination af drenge - Effekt på anogenitale infektioner og cancere

    DEFF Research Database (Denmark)

    Roed, Michelle S.; Nielsen, Anni Brit Sternhagen; Aabenhus, Rune Munck

    2013-01-01

    HPV-vaccination tilbydes alle piger, men skal HPV-vaccinationen også tilbydes drenge? Det undersøger forfatterne i denne artikel ved at kigge litteraturen igennem. Konklusionen er, at der nok også er effekt på en række af de HPV-relaterede sygdomme hos drenge/mænd. Der mangler imidlertid fortsat...... viden om varighed af vaccinationseffekten – og om de økonomiske konsekvenser af at indføre vaccinationen blandt drenge....

  1. Gene Painting as a Simple Method for Vaccinating Animals Against Breast Cancer Micro-Metastases

    Science.gov (United States)

    2001-10-01

    Program Phase I grant (#N00014-01-M-0178): "Needleless topical administration of dengue DNA vaccine", $69,000 Preceptor, 2000-2001, Dermatology...sites at the ends of the 1.35-kb TetC fragment with a synthetic eukaryotic ribosomal binding site (13) inserted in frame. The PCR-amplified fragment...application of tumor epitope peptides (17), it has not been demonstrated, prior to our studies, that a patho- gen of human relevance could be arrested

  2. Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer Who Received Chemotherapy

    Science.gov (United States)

    2016-11-29

    Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  3. Biodistribution profiles of recombinant anti-breast cancer immunotherapeutic infusion protein HSP-MUC1 vaccine after subcutaneous in tumor-bearing mice

    Institute of Scientific and Technical Information of China (English)

    JingBAI; Hai-fengSONG; Xiu-wenLIU; Bao-zhenZHU; LunOU; XiaoSUN; Xiao-junMIAO

    2004-01-01

    AIM: To study biodistributional profiles of recombinant antibreast cancer immunotherapeutic fusion protein HSP-MUC1 vaccine after subcutaneous in tumor-bearing mice. METHODS: HSP-MUC1 of variant tissue was detected by 125I-HSP-MUC1 combined with trichloroacetic acid (TCA) precipitation or sizeexclusive high performance liquid chromatography (SHPLC). RESULTS: 125I-HSP-MUC1 distributed widely. The highest

  4. Immunological evaluation of peptide vaccination for cancer patients with the HLA -A11(+) or -A33(+) allele.

    Science.gov (United States)

    Sakamoto, Shijoro; Matsueda, Satoko; Takamori, Shinzou; Toh, Uhi; Noguchi, Masanori; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Yamada, Teppei; Suekane, Shigetaka; Kawano, Kouichirou; Naitou, Masayasu; Sasada, Tetsuro; Hattori, Noboru; Kohno, Nobuoki; Itoh, Kyogo

    2017-02-08

    The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11(+) /A11(+) (n=18) or -A33(+) /A33(+) (n=13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n=4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas(2 or 2), and so on. For PPV, a maximum of 4 peptides were selected from 9 different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11(+) /A11(+) or -A33(+) /A33(+) patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of 4 stable diseases and 14 progressive diseases in HLA-A11(+) /A11(+) patients, versus 7 and 6 in -A33(+) /A33(+) patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses. This article is protected by copyright. All rights reserved.

  5. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2014-10-01

    will produce a set of immunologically validated antigens and mimotopes for major breast cancer subtypes, and a set of agents that cooperate with... immunologic target, the remaining transcripts undergo epitope candidate ranking (Fig. 2) to take the length of the potential epitope into account...particular is associated with supporting hepatic cancer progression through targeting of PTEN [20]. The cellular retinoic acid binding protein (CRABP2) is

  6. Why HPV Vaccine is Important to My Family: The Story of a Cervical Cancer Survivor

    Centers for Disease Control (CDC) Podcasts

    2013-05-06

    A young mom’s world is turned upside-down when she’s diagnosed with cervical cancer. Learn what she’s doing to protect her kids from HPV-related cancers.  Created: 5/6/2013 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/6/2013.

  7. ELISPOT Assay for Monitoring Cytotoxic T Lymphocytes (CTL Activity in Cancer Vaccine Clinical Trials

    Directory of Open Access Journals (Sweden)

    Thomas J. Sayers

    2012-05-01

    Full Text Available The profiling and monitoring of immune responses are key elements in the evaluation of the efficacy and development of new biotherapies, and a number of assays have been introduced for analyzing various immune parameters before, during, and after immunotherapy. The choice of immune assays for a given clinical trial depends on the known or suggested immunomodulating mechanisms associated with the tested therapeutic modality. Cell-mediated cytotoxicity represents a key mechanism in the immune response to various pathogens and tumors. Therefore, the selection of monitoring methods for the appropriate assessment of cell-mediated cytotoxicity is thought to be crucial. Assays that can detect both cytotoxic T lymphocytes (CTL frequency and function, such as the IFN-γ enzyme-linked immunospot assay (ELISPOT have gained increasing popularity for monitoring clinical trials and in basic research. Results from various clinical trials, including peptide and whole tumor cell vaccination and cytokine treatment, have shown the suitability of the IFN-γ ELISPOT assay for monitoring T cell responses. However, the Granzyme B ELISPOT assay and Perforin ELISPOT assay may represent a more direct analysis of cell-mediated cytotoxicity as compared to the IFN-γ ELISPOT, since Granzyme B and perforin are the key mediators of target cell death via the granule-mediated pathway. In this review we analyze our own data and the data reported by others with regard to the application of various modifications of ELISPOT assays for monitoring CTL activity in clinical vaccine trials.

  8. Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

    Science.gov (United States)

    2017-01-24

    Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

  9. Research progress of vaccine therapy in non-small cell lung cancer%非小细胞肺癌疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    石岳泉(综述); 魏敏杰(审校)

    2015-01-01

    相比手术、放化疗等常规治疗手段和近年来热门的基因靶向疗法,免疫治疗,特别是肺癌疫苗疗法具有不良反应少、治疗成本低的优点。随着对免疫系统和肿瘤抗原表达情况的进一步了解,多种非小细胞肺癌(non-small cell lung cancer,NSCLC)疫苗的Ⅲ期临床试验正在逐渐开展。本文将对NSCLC中最具临床应用潜力疫苗的发展情况及相关临床试验的进展进行综述。%Immunotherapy, particularly lung cancer vaccine therapy, has advantages of less side effects and low costs over classi-cal therapies of lung cancer, such as surgery, radiotherapy, and chemotherapy, as well as the relatively new molecular targeting therapy. PhaseⅢclinical trial for many kinds of non-small cell lung cancer (NSCLC) vaccines is ongoing based on deeper understanding of im-mune system and the expression of tumor antigens. This review summarizes the development of NSCLC vaccines.

  10. Cervical Cancer Prevention in Malaysia: Knowledge and Attitude of Undergraduate Pharmacy Students Towards Human Papillomavirus Infection, Screening and Vaccination in Malaysia.

    Science.gov (United States)

    Maharajan, Mari Kannan; Rajiah, Kingston; Sze Fang, Kelly Num; Lui, Lai Yun

    2017-03-01

    This study was conducted to evaluate knowledge of undergraduate pharmacy students about human papillomavirus infection and their attitude towards its prevention. A cross-sectional survey was conducted in 270 undergraduate pharmacy students using a validated questionnaire to assess knowledge about human papillomavirus infection and cervical cancer and their attitudes towards human papillomavirus vaccines. Eighty-one percent of the respondents knew that human papillomavirus is a cause of cervical cancer, and 87.8 % knew that this infection is preventable. The gender of the respondents showed the strongest correlations with human papillomavirus knowledge. There were no significant correlations between the ethnic group of the respondents and their human papillomavirus-related knowledge. Higher perceptions of risk were associated with relationship status, and respondents who were in a relationship showed greater interest in vaccinating themselves; relationship status emerged as a unique predictor. The results indicated a moderately high level of knowledge and positive attitude towards human papillomavirus vaccination with few disagreements. The results of this study will help to develop and plan appropriate education campaigns for pharmacy students that aim to reduce human papillomavirus infection and, consequently, the incidence of and mortality caused by cervical cancer in Malaysia.

  11. Key Facts about Seasonal Flu Vaccine

    Science.gov (United States)

    ... Cancer Parents Children, the Flu, and the Flu Vaccine Children and Flu Antiviral Drugs Caregivers of Young Children ... older adults. A 2014 study * showed that flu vaccine reduced children’s risk of flu-related pediatric intensive care unit ( ...

  12. 宫颈癌治疗性疫苗的临床研究现状%Advances in the clinical research of therapeutic vaccines for cervical cancer

    Institute of Scientific and Technical Information of China (English)

    张立娜; 周志祥; 盛望; 曾毅

    2012-01-01

    Human papillomavirus (HPV) is a major etiological factor in cervical cancer, and it provides a promising target for the eradication of HPV-related malignancies. Although preventive HPV vaccines have been approved, the much-needed therapeutic vaccines targeted to HPV for cervical cancer require further development. Currently, a number of therapeutic vaccines have been developed and many have shown promise in both preclinical and clinical trials. This review discusses the therapeutic vaccines including live vector-based, peptide or protein-based, DNA-based and DC-based vaccines with emphasis on current progress of the clinical trials.%人乳头瘤状病毒(human papillomavirus,HPV)是宫颈癌的主要致病因子,也是研制宫颈癌防治性疫苗的理想靶点.虽然现在针对HPV感染的宫颈癌预防性疫苗已成功上市,但是对于急需的治疗型疫苗的研发还在进行中.目前有多种类型的治疗性疫苗已用于临床前期及临床试验,并显示出很好的治疗效果.本文从活载体疫苗、多肽/蛋白疫苗、DNA疫苗和DC疫苗几个方面综述了目前国内外宫颈癌治疗性疫苗的研究现状及进展,特别是进入临床阶段的疫苗,从而为治疗性疫苗的研究提供参考.

  13. Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients.

    Science.gov (United States)

    Odunsi, Kunle; Matsuzaki, Junko; Karbach, Julia; Neumann, Antje; Mhawech-Fauceglia, Paulette; Miller, Austin; Beck, Amy; Morrison, Carl D; Ritter, Gerd; Godoy, Heidi; Lele, Shashikant; duPont, Nefertiti; Edwards, Robert; Shrikant, Protul; Old, Lloyd J; Gnjatic, Sacha; Jäger, Elke

    2012-04-10

    Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4(+) and CD8(+) T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0-84 mo) and the median OS was 48 mo (range, 3-106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16-29 mo), and median OS was 48 mo (CI, not estimable). CD8(+) T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.

  14. Therapeutic dendritic cell-based cancer vaccines: the state of art

    NARCIS (Netherlands)

    Strioga, M.M.; Felzmann, T.; Powell, D.J.; Ostapenko, V.; Dobrovolskiene, N.T.; Matuskova, M.; Michalek, J.; Schijns, V.E.J.C.

    2013-01-01

    Dendritic cells (DCs) are the most potent professional antigen-presenting cells, capable of initiating proper adaptive immune responses. Although tumor-infiltrating DCs are able to recognize cancer cells and uptake tumor antigens, they often have impaired functions because of the immunosuppressive t

  15. Economic Evaluation of Screening Strategies Combined with HPV Vaccination of Preadolescent Girls for the Prevention of Cervical Cancer in Vientiane, Lao PDR

    Science.gov (United States)

    2016-01-01

    Background Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options. Objective To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR. Methods A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA), cytology-based screening, rapid human papillomavirus (HPV) DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY) averted. Results In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30–65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$) per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively. Conclusions A VIA screening program

  16. A novel chimeric flagellum fused with the multi-epitope vaccine CTB-UE prevents Helicobacter pylori-induced gastric cancer in a BALB/c mouse model.

    Science.gov (United States)

    Song, Hui; Lv, Xiaobo; Yang, Jue; Liu, Wei; Yang, Huan; Xi, Tao; Xing, Yingying

    2015-11-01

    Helicobacter pylori (H. pylori) infection causes peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. The eradication of H. pylori might be an effective means of preventing gastric cancer. A dual-antigen epitope and dual-adjuvant vaccine called CTB-UE-CF (CCF) was constructed by combining a multi-epitope vaccine CTB-UE with a novel chimeric flagellum (CF) to simultaneously activate Toll-like receptor (TLR) 5-agonist activity and preserve the immunogenicity of H. pylori flagellum FlaA. The evaluation of efficacy to reduce H. pylori colonization was performed using BALB/c mice by oral immunization with a triple dose of this vaccine strain. Two weeks after the last immunization, mice were sacrificed to determine specific antibody levels and proinflammatory cytokine production. To determine the presence of H. pylori, we detected the number of H. pylori by real-time quantitative PCR (qPCR) and measured the urease activity in the gastric tissue. The results showed that the immunogenicity and mucosal immune responses of CCF performed significantly better than those of CTB-UE. This dual-antigen epitope and dual-adjuvant system might greatly contribute to the development of a safe and efficient therapeutic vaccine for humans against H. pylori infection.

  17. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  18. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  19. Global challenges of implementing human papillomavirus vaccines

    Directory of Open Access Journals (Sweden)

    Mishra Amrita

    2011-06-01

    Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

  20. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    ... Human Papillomavirus (HPV) Nonavalent Vaccine Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine Drugs Approved to Treat Cervical Cancer Avastin (Bevacizumab) Bevacizumab Blenoxane (Bleomycin) Bleomycin Hycamtin (Topotecan ...

  1. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  2. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  3. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer

    Science.gov (United States)

    Lizotte, P. H.; Wen, A. M.; Sheen, M. R.; Fields, J.; Rojanasopondist, P.; Steinmetz, N. F.; Fiering, S.

    2016-03-01

    Nanotechnology has tremendous potential to contribute to cancer immunotherapy. The ‘in situ vaccination’ immunotherapy strategy directly manipulates identified tumours to overcome local tumour-mediated immunosuppression and subsequently stimulates systemic antitumour immunity to treat metastases. We show that inhalation of self-assembling virus-like nanoparticles from cowpea mosaic virus (CPMV) reduces established B16F10 lung melanoma and simultaneously generates potent systemic antitumour immunity against poorly immunogenic B16F10 in the skin. Full efficacy required Il-12, Ifn-γ, adaptive immunity and neutrophils. Inhaled CPMV nanoparticles were rapidly taken up by and activated neutrophils in the tumour microenvironment as an important part of the antitumour immune response. CPMV also exhibited clear treatment efficacy and systemic antitumour immunity in ovarian, colon, and breast tumour models in multiple anatomic locations. CPMV nanoparticles are stable, nontoxic, modifiable with drugs and antigens, and their nanomanufacture is highly scalable. These properties, combined with their inherent immunogenicity and demonstrated efficacy against a poorly immunogenic tumour, make CPMV an attractive and novel immunotherapy against metastatic cancer.

  4. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact.

  5. Self-replicating alphavirus RNA vaccines.

    Science.gov (United States)

    Ljungberg, Karl; Liljeström, Peter

    2015-02-01

    Recombinant nucleic acids are considered as promising next-generation vaccines. These vaccines express the native antigen upon delivery into tissue, thus mimicking live attenuated vaccines without having the risk of reversion to pathogenicity. They also stimulate the innate immune system, thus potentiating responses. Nucleic acid vaccines are easy to produce at reasonable cost and are stable. During the past years, focus has been on the use of plasmid DNA for vaccination. Now mRNA and replicon vaccines have come into focus as promising technology platforms for vaccine development. This review discusses self-replicating RNA vaccines developed from alphavirus expression vectors. These replicon vaccines can be delivered as RNA, DNA or as recombinant virus particles. All three platforms have been pre-clinically evaluated as vaccines against a number of infectious diseases and cancer. Results have been very encouraging and propelled the first human clinical trials, the results of which have been promising.

  6. Get Vaccinated! and Get Tested! Developing Primary and Secondary Cervical Cancer Prevention Videos for a Haitian Kreyòl-Speaking Audience.

    Science.gov (United States)

    Frett, Brigitte; Aquino, Myra; Fatil, Marie; Seay, Julia; Trevil, Dinah; Fièvre, Michèle Jessica; Kobetz, Erin

    2016-05-01

    Although routine screening reduces cervical cancer rates between 60% and 90%, thousands of women worldwide are diagnosed with the disease on an annual basis because of inadequate screening. Haitian women in South Florida experience a disproportionate burden of cervical cancer, with disease rates 4 times higher than the average for women in Miami. An ongoing community-based participatory research initiative to assess and reduce this burden has revealed that a complex interplay of factors contributes to a lack of access to screening in this community, including socioeconomics, language barriers, and traditional understandings of health and disease. In an effort to address some of these barriers and encourage uptake of primary and secondary cervical cancer prevention strategies, 2 videos on cervical cancer prevention were created using a community-based participatory research framework. The video screenplays were created by a Haitian screenwriter using evidence-based medical information provided by academic researchers. The films feature Haitian actors speaking a Haitian Kreyòl dialogue with a storyline portraying friends and family discussing human papillomavirus disease and vaccination, Papanicolaou testing, and cervical cancer. Focus groups held with Haitian women in South Florida suggested that the films are engaging; feature relatable characters; and impact knowledge about human papillomavirus, cervical cancer development, and current prevention recommendations.

  7. Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Nikolajsen, Kirsten;

    2008-01-01

    We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201 binding wild-type p53 derived peptides. This vaccine was used in combination with low-dose interleukin-2 in a recently published clinical...... Phase II trial where 26 HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were included. Almost 1/3rd of the patients obtained stable disease or minor regression during treatment with a positive correlation to tumour over-expression of p53. In the present study, we performed...... (CD44high, CCR-7low and CD62Llow). Furthermore, fresh blood from 18 cancer patients included in the vaccination trial were prospectively examined for more general treatment associated quantitative and qualitative changes in T cell subpopulations. We found that the frequency of CD4+ CD25high regulatory...

  8. Understanding the biology of antigen cross-presentation for the design of vaccines against cancer.

    Science.gov (United States)

    Fehres, Cynthia M; Unger, Wendy W J; Garcia-Vallejo, Juan J; van Kooyk, Yvette

    2014-01-01

    Antigen cross-presentation, the process in which exogenous antigens are presented on MHC class I molecules, is crucial for the generation of effector CD8(+) T cell responses. Although multiple cell types are being described to be able to cross-present antigens, in vivo this task is mainly carried out by certain subsets of dendritic cells (DCs). Aspects such as the internalization route, the pathway of endocytic trafficking, and the simultaneous activation through pattern-recognition receptors have a determining influence in how antigens are handled for cross-presentation by DCs. In this review, we will summarize new insights in factors that affect antigen cross-presentation of human DC subsets, and we will discuss the possibilities to exploit antigen cross-presentation for immunotherapy against cancer.

  9. Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer; monitoring of serum YKL-40 and IL-6 as response biomarkers

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Johansen, Julia S;

    2007-01-01

    p53 Mutations are found in up to 30% of breast cancers and peptides derived from over-expressed p53 protein are presented by class I HLA molecules and may act as tumor-associated epitopes in cancer vaccines. A dendritic cell (DC) based p53 targeting vaccine was analyzed in HLA-A2+ patients...... with progressive advanced breast cancer. DCs were loaded with 3 wild-type and 3 P2 anchor modified HLA-A2 binding p53 peptides. Patients received up to 10 sc vaccinations with 5 x 10(6) p53-peptide loaded DC with 1-2 weeks interval. Concomitantly, 6 MIU/m(2) interleukine-2 was administered sc. Results from a phase...... II trial including 26 patients with verified progressive breast cancer are presented. Seven patients discontinued treatment after only 2-3 vaccination weeks due to rapid disease progression or death. Nineteen patients were available for first evaluation after 6 vaccinations; 8/19 evaluable patients...

  10. Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers

    OpenAIRE

    2000-01-01

    Cancer–testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40–50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody neg...

  11. MAGE基因在肺癌疫苗研究进展%Research progress of MAGE gene in lung cancer vaccine

    Institute of Scientific and Technical Information of China (English)

    刘帮助; 刘超

    2012-01-01

    As the tumor to evade immune surveillance mechanism for the continuous in-depth research,immunotherapy has become a promising new method for treatment of cancer. One cancer vaccine as a tumor-specific active immunotherapy of lung cancer becomes a very attractive strategy of targeted therapy,especially for patients with completely resected adjuvant therapy. In recent years,cancer vaccines is the use of MAGE peptides,genes,and dendritic cells in patients with lung cancer,tumor immune response and mitigation have been observed in phase Ⅰ / Ⅱ clinical trials,and good clinical evaluation achieved.Ongoing international multi-center clinical study will demonstrate it.%随着对肿瘤逃避免疫监视机制研究的不断深入,免疫治疗已成为一种有希望治疗肿瘤的新方法.其中肿瘤疫苗作为肿瘤的特异性主动免疫治疗成为肺癌非常有吸引力的靶向治疗策略之一,尤其适用于完全切除术后患者的辅助治疗.近年来肿瘤疫苗是采用MAGE多肽、基因和树突状细胞等方法来免疫肺癌患者,在Ⅰ/Ⅱ期临床试验中已观察到免疫反应和肿瘤的缓解,并取得了较好的临床疗效评价.目前正在进行国际多中心临床研究进行论证.

  12. 人乳头瘤病毒疫苗预防宫颈癌的应用%Application of HPV Vaccines in Preventing Development of the Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    夏巧凡; 何莲芝

    2015-01-01

    Cervical cancer causes serious damage to women′s health. It is clear that human papillomavirus (HPV) infection is the major pathogenic factor. HPV invades the organism by subtle injures. When E6 or E7 oncoprotein is continous expression in the epithelial tissue, high-risk HPV infections contribute to tumorigenicity. Detection of high-risk HPV infection and virus oncoprotein still cannot prevent cervical cancer effectively. Researchers begin to develop a vaccine against the HPV virus, and to prevent HPV infections from the sources, hoping to achieve the primary prevention of cervical cancer. Currently bivalent vaccine Cervarix against HPV 16/18 and quadrivalent vaccine Gardasil against HPV 16/18/11/16 have been approved for marketing. Prophylactic HPV vaccines have been used widely on a global scale and obtained significant effect. A new generation of prophylactic HPV vaccines have made a breakthrough in solving problems including cost, persistence and broad-spectrum immune. Cervical cancer is expected to become the first preventable cancer in the history of human anti-tumor. This review concentrates on the biological characteristics and pathogenic mechanism of HPV and the current application and situation of prophylactic HPV vaccines.%宫颈癌严重危害女性健康,现已明确人乳头瘤病毒(HPV)感染是其主要致病因素。HPV通过机体的细微损伤入侵,HPV E6和E7癌蛋白中的1种或2种持续表达是高危型HPV感染致瘤的关键所在,检测高危型HPV感染及病毒癌蛋白仍不能有效预防宫颈癌。研究者们正着手研制针对HPV的病毒疫苗,从源头预防HPV感染,以期实现宫颈癌的一级预防。目前已有针对HPV16/18型的二价疫苗Cervarix和针对HPV16/18/11/6型的四价疫苗Gardasil的认证上市,预防性HPV疫苗已在全球范围内推广使用并取得显著效果。新一代预防性HPV疫苗在解决疫苗的成本、持久性和广谱免疫问题上取得突破性进展,

  13. Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC

    Directory of Open Access Journals (Sweden)

    Jay Overholser

    2015-07-01

    Full Text Available Despite the promise of targeted therapies, there remains an urgent need for effective treatment for esophageal cancer (EC and triple-negative breast cancer (TNBC. Current FDA-approved drugs have significant problems of toxicity, safety, selectivity, efficacy and development of resistance. In this manuscript, we demonstrate that rationally designed peptide vaccines/mimics are a viable therapeutic strategy for blocking aberrant molecular signaling pathways with high affinity, specificity, potency and safety. Specifically, we postulate that novel combination treatments targeting members of the EGFR family and IGF-1R will yield significant anti-tumor effects in in vitro models of EC and TNBC possibly overcoming mechanisms of resistance. We show that the combination of HER-1 and HER-2 or HER-1 and IGF-1R peptide mimics/vaccine antibodies exhibited enhanced antitumor properties with significant inhibition of tumorigenesis in OE19 EC and MDA-MB-231 TNBC cell lines. Our work elucidates the mechanisms of HER-1/IGF-1R and HER-1/HER-2 signaling in these cancer cell lines, and the promising results support the rationale for dual targeting with HER-1 and HER-2 or IGF-1R as an improved treatment regimen for advanced therapy tailored to difference types of cancer.

  14. Therapeutic targeting of liver cancer with a recombinant DNA vaccine containing the hemagglutinin-neuraminidase gene of Newcastle disease virus via apoptotic-dependent pathways.

    Science.gov (United States)

    Chen, Li-Gang; Liu, Yuan-Sheng; Zheng, Tang-Hui; Chen, Xu; Li, Ping; Xiao, Chuan-Xing; Ren, Jian-Lin

    2016-11-01

    A total of ~38.6 million mortalities occur due to liver cancer annually, worldwide. Although a variety of therapeutic methods are available, the efficacy of treatment at present is extremely limited due to an increased risk of malignancy and inherently poor prognosis of liver cancer. Gene therapy is considered a promising option, and has shown notable potential for the comprehensive therapy of liver cancer, in keeping with advances that have been made in the development of cancer molecular biology. The present study aimed to investigate the synergistic effects of the abilities of the hemagglutinin neuraminidase protein of Newcastle disease virus (NDV), the pro-apoptotic factor apoptin from chicken anaemia virus, and the interferon-γ inducer interleukin-18 (IL-18) in antagonizing liver cancer. Therefore, a recombinant DNA plasmid expressing the three exogenous genes, VP3, IL-18 and hemagglutinin neuraminidase (HN), was constructed. Flow cytometry, acridine orange/ethidium bromide staining and analysis of caspase-3 activity were performed in H22 cell lines transfected with the recombinant DNA plasmid. In addition, 6-week-old C57BL/6 mice were used to establish a H22 hepatoma-bearing mouse model. Mice tumor tissue was analyzed by immunohistochemistry and scanning electron microscopy. The results of the present study revealed that the recombinant DNA vaccine containing the VP3, IL-18 and HN genes inhibited cell proliferation and induced autophagy via the mitochondrial pathway in vivo and in vitro.

  15. Status of a Unique Vaccine against hCG for Contraception and Advanced Stage Cancers expressing ectopically hCG

    Directory of Open Access Journals (Sweden)

    Talwar GP

    2015-01-01

    Full Text Available Dear Egon!br God bless you on your 95th Birthday! May you complete 100 years.br Being submitted in your honor is a brief article on my continuing work to make available a unique vaccine preventing pregnancy in women without blocking ovulation, her normal production of sex steroid hormones and retaining her regular menstrual cycles and bleeding profiles.br The vaccine is directed at the Human chorionic gonadotropin (hCG, which emerges following fertilization of the egg [1]. Healthy, non-pregnant women do not make it, the basis on which its detection in serum or urine serves as a reliable test for diagnosis of pregnancy. It plays a critical role in implantation of the embryo & thereby to the onset of pregnancy. The purpose of the vaccine is to generate bioeffective antibodies neutralizing hCG & thereby prevent the onset of pregnancy.br As you can imagine, the making of a workable vaccine, competent to make antibodies against a tolerant molecule to the woman’s immune system (she literally bathes in hCG during pregnancy was not simple. What was also demanded was high immunogenicity of the vaccine to make fairly high titres of antibodies to counteract the large amount of hCG made in early pregnancy. At each stage, it required testing in humans and before that could be done, appropriate toxicology studies & approval of Regulatory and Ethics Committees was needed each taking its time. Eventually the vaccine has to be amenable to industrial production to reach the public, hence a recombinant vaccine had to be developed. Given below is a brief write-up on the evolution of the vaccine against the human chorionic gonadotropin.br Yours, Pran

  16. B Cell Epitope-Based Vaccination Therapy

    Directory of Open Access Journals (Sweden)

    Yoshie Kametani

    2015-08-01

    Full Text Available Currently, many peptide vaccines are undergoing clinical studies. Most of these vaccines were developed to activate cytotoxic T cells; however, the response is not robust. Unlike vaccines, anti-cancer antibodies based on passive immunity have been approved as a standard treatment. Since passive immunity is more effective in tumor treatment, the evidence suggests that limited B cell epitope-based peptide vaccines may have similar activity. Nevertheless, such peptide vaccines have not been intensively developed primarily because humoral immunity is thought to be preferable to cancer progression. B cells secrete cytokines, which suppress immune functions. This review discusses the possibility of therapeutic antibody induction by a peptide vaccine and the role of active and passive B cell immunity in cancer patients. We also discuss the use of humanized mice as a pre-clinical model. The necessity of a better understanding of the activity of B cells in cancer is also discussed.

  17. Cervical cancer - screening and prevention

    Science.gov (United States)

    Cancer cervix - screening; HPV - cervical cancer screening; Dysplasia - cervical cancer screening; Cervical cancer - HPV vaccine ... Almost all cervical cancers are caused by HPV (human papilloma virus). HPV is a common virus that spreads through sexual contact. Certain ...

  18. Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded dendritic cell vaccine in vitro

    Directory of Open Access Journals (Sweden)

    Wang S

    2014-08-01

    Full Text Available Shuo Wang,1 Yonghua Wang,1 Jing Liu,2 Shixiu Shao,1 Xianjun Li,1 Jiannan Gao,1 Haitao Niu,1 Xinsheng Wang1 1Department of Urology, 2Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China Objective: The aim of this study was to examine whether short hairpin RNA (shRNA expressing lentiviral particles targeting B7-H1 infection could result in B7-H1 knockdown on dendritic cells (DCs and to investigate whether B7-H1 silencing could augment the immune function of DCs and further elicit a more potent anti-tumor immune effect against bladder cancer cells in vitro. Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells, were infected by a recombinant lentivirus containing shRNA sequence aimed at B7-H1. After that, the infected DCs were pulsed by tumor antigens and used to stimulate cytotoxic T lymphocytes-based anti-tumor effect in vitro. Results: The lentivirus-mediated shRNA delivery method efficiently and effectively silenced B7-H1 in DCs. Furthermore, the B7-H1 silencing enhanced the stimulatory capacity and the secretion of interleukin-12, but down-regulated interleukin-10 secretion. And more importantly, the anti-tumor effect of bladder cancer antigen-loaded DC vaccine in vitro was also potentially augmented. Conclusion: This study suggests that a combination of B7-H1 knockdown and target antigen delivery could augment anti-tumor effects in vitro, which potentially provides a novel strategy in the immunotherapy of bladder cancer. Keywords: B7-H1, bladder cancer, dendritic cell, vaccine, immunotherapy

  19. How One Clinic Got a Big Boost in HPV Vaccination Rates

    Science.gov (United States)

    ... One Clinic Got a Big Boost in HPV Vaccination Rates The cervical cancer vaccine was treated as ... the United States, lagging far behind other recommended vaccinations in this age group. But, by lumping HPV ...

  20. Variable epitope library carrying heavily mutated survivin-derived CTL epitope variants as a new class of efficient vaccine immunogen tested in a mouse model of breast cancer.

    Science.gov (United States)

    NoeDominguez-Romero, Allan; Zamora-Alvarado, Rubén; Servín-Blanco, Rodolfo; Pérez-Hernández, Erendira G; Castrillon-Rivera, Laura E; Munguia, Maria Elena; Acero, Gonzalo; Govezensky, Tzipe; Gevorkian, Goar; Manoutcharian, Karen

    2014-01-01

    The antigenic variability of tumor cells leading to dynamic changes in cancer epitope landscape along with escape from immune surveillance by down-regulating tumor antigen expression/presentation and immune tolerance are major obstacles for the design of effective vaccines. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response as well as HIV-neutralizing antibodies. In this proof-of-concept study, we tested immunogenic properties and anti-tumor effects of the VELs bearing survivin-derived CTL epitope (GWEPDDNPI) variants in an aggressive metastatic mouse 4T1 breast tumor model. The constructed VELs had complexities of 10,500 and 8,000 individual members, generated as combinatorial M13 phage display and synthetic peptide libraries, respectively, with structural composition GWXPXDXPI, where X is any of 20 natural amino acids. Statistically significant tumor growth inhibition was observed in BALB/c mice immunized with the VELs in both prophylactic and therapeutic settings. Vaccinated mice developed epitope-specific spleen cell and CD8+ IFN-γ+ T-cell responses that recognize more than 50% of the panel of 87 mutated epitope variants, as demonstrated in T-cell proliferation assays and FACS analysis. These data indicate the feasibility of the application of this new class of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against cancer.

  1. 宫颈癌治疗性疫苗临床研究进展%Clinical research advance in therapeutic vaccines against cervical cancer

    Institute of Scientific and Technical Information of China (English)

    黄云霞

    2012-01-01

    Persistent infection by high-risk human papillomavirus (HPV) has been found associated with most cervical cancers.With the further study on HPV and its pathogenic mechanism,several therapeutic vaccines against cervical cancer have been developed,and even in clinical trial phrase.In this paper,the progress in clinical trials and design strategies of therapeutic HPV vaccines are reviewed.%宫颈癌的发生与高危型人乳头瘤病毒( human papillomavirus,HPV)的持续感染有关.随着对HPV及其致病机制的深入研究,已经开发了多种用于宫颈癌生物免疫治疗的疫苗,有些已进入临床试验.此文对已进入临床试验阶段的宫颈癌疫苗的设计策略和临床试验进展做一综述.

  2. French women’s knowledge of and attitudes towards cervical cancer prevention and the acceptability of HPV vaccination among those with 14 – 18 year old daughters: a quantitative-qualitative study

    Directory of Open Access Journals (Sweden)

    Haesebaert Julie

    2012-11-01

    Full Text Available Abstract Background In France, it is recommended that girls and women aged 14–23 are vaccinated against the human papillomavirus (HPV. However, French women’s knowledge of and attitude towards the vaccine has been little studied. Methods Thirty-nine general practitioners, representative of those working in the large Rhône-Alpes region, offered a self-administered questionnaire on cervical cancer (CC prevention to all 18–65 year-old women who came for consultation during June and July 2008. In addition, semi-structured interviews were undertaken with a sample of those who had daughters aged 14–18. Results Of the 1,478 women who completed the questionnaire, only 16.9% mentioned HPV as the cause of CC, even though 76.2% knew of the vaccine. 210 women had daughters aged 14–18, and 32 were interviewed. Compared with the wider group, more of these women were aware of the HPV vaccine (91.4%. 44.8% knew the target population and 17.1% the recommended ages for vaccination. 54.3% favoured HPV vaccination; 37.2% were undecided and only 0.9% were opposed. The main barrier to acceptance was the recency of the vaccine’s introduction and concern about possible side effects (54.9%; 14.1% preferred to rely on their GP’s decision. Factors associated with acceptance of the HPV vaccine were having previously vaccinated a child against pneumococcus (OR=3.28 [1.32-8.11] and knowing the target population for HPV vaccination (OR=2.12 [1.15-3.90]. Knowing the recommended frequency of Papanicolaou smear testing (Pap test screening was associated with lower acceptance (OR=0.32 [0.13-0.82]. Conclusions Few mothers are opposed to HPV vaccination. Factors associated with acceptability were knowledge about the vaccine, acceptance of other vaccines and, unexpectedly, lack of knowledge about the recommended frequency of Pap testing. On multivariate analysis, compliance with recommendations for Pap test screening and socioeconomic factors had no effect on views

  3. Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer.

    Science.gov (United States)

    Gardner, Thomas A; Elzey, Bennett D; Hahn, Noah M

    2012-04-01

    Sipuleucel-T (Provenge) (Sip-T) is first -in class as a therapeutic autologous vaccine approved for the treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. This product is the culmination of decades of basic immunological and prostate cancer investigations and 13 y of clinical trial investigations. Sip-T represents a paradigm shift in cancer therapeutics and represents the first approved autologous therapeutic cancer vaccine, which has demonstrated a survival benefit. The potential benefit of this product is the excellent risk to benefit ratio, which will allow for the combination of this approach with other more toxic therapies. The favorable risk to benefit will also afford the opportunity for trials investigating this product earlier in the disease state and in combination with local therapies. The ability to target more localized or lower volume disease will maximize the therapeutic benefit over a longer period of time. The novelty of the platform of this approach could be used to treat any cancer with a tumor-specific cell surface target. The main product of Sip-T is the re-infusion of a patient's antigen presenting cells from leukapheresis after ex-vivo exposure to a chimeric protein of human GM-CSF and PAP. In metastatic CRPC patients three infusions of these activated cells over a month lead to statistically significant 4.1 mo increase in median survival and a 22.5% reduction in risk of death. The main side effect from this re-infusion of activated immune cells is a "flu-like" syndrome that includes chills, fatigue, fevers, back pain, nausea, joints aches and headaches in decreasing order of frequency. Immune monitoring during the clinical trials also demonstrated a specific cellular and antibody immune response, suggesting the proposed mechanism of adoptive immunotherapy to PAP was behind this survival benefit. This product also serves as a proof of principle for targeted immunotherapy for others

  4. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  5. Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.

    Science.gov (United States)

    Singh, Manisha; Ramos, Ilyssa; Asafu-Adjei, Denise; Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Zang, Xingxing; Aggarwal, Bharat B; Gravekamp, Claudia

    2013-08-01

    Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeria(at)), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeria(at)-Mage-b and curcumin were tested. The first immunization strategy involved all Listeria(at)-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeria(at)-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeria(at)-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeria(at)-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression.

  6. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  7. 树突细胞肿瘤疫苗用于治疗胃肠管恶性肿瘤的研究进展%Research progress of dendritic cells based cancer vaccines against gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    胡健卫; 牛伟新

    2008-01-01

    胃肠管恶性肿瘤是人类最常见的恶性肿瘤.在目前以手术切除为主的综合治疗中,传统放、化疗由于其治疗模式的非特异性特点,常难以达到理想的结果.树突状细胞(dendritic cell,DC)肿瘤疫苗作为近年来兴起的一个免疫治疗新方法,被越来越多地应用到临床试验中,在用于治疗胃肠管恶性肿瘤中也取得了一些效果.虽然目前疫苗的设计尚无公认的标准,且其免疫学效果和临床预后也未能取得正相关的联系,但对DC免疫机制的深入了解和相应新方法的研究有可能在治疗恶性肿瘤方面发挥更大的作用.%Gastrointestinal cancers are the most common types of malignant tumors in Human Beings.The main treatment remains surgery resection,in addition to which,adjunctive therapies are far not satisfactory for the target of which are not specific.Dendritic cells cancer vaccine is one of the most promising immunotherapy ways developed in the decades and some results have showed that the vaccines may help in the treatment of gastrointestinal cancers.Till now,there is no recognized standard in the design of the vaccine and no positive correlations between the immunologic effect and clinical prognosis are showed,but we believe that with the further research in the immunological mechanism and the use of new designed methods,dendritic cells cancer vaccines will play a greater role in the treatment of malignant tumors.

  8. The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling

    DEFF Research Database (Denmark)

    Met, Ozcan; Wang, Mingjun; Pedersen, Anders E

    2006-01-01

    Dendritic cells (DCs) were pulsed with the H-2K(b) binding OVA(257-264)-peptide (SIINFEKL), and used as one single-injection vaccine in combination with anti-CTLA-4 monoclonal antibody (mAb) to treat mice inoculated 3 days previously with 3x10(5) E.G7-OVA lymphoma cells. Neither DC vaccination nor...... CTLA-4 blockage alone prevented tumor growth in tumor challenged mice. In contrast, the combination of one vaccination and injection of anti-CTLA-4 mAb lead to rejection or retarded tumor growth in more than 60% of the mice. The OVA-transgene or the SIINFEKL-epitope was not lost in the progressing...

  9. Rabies Vaccine

    Science.gov (United States)

    ... high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers should be offered rabies vaccine. The vaccine should also be considered for: (1) ...

  10. Edible vaccines.

    OpenAIRE

    Artnzen, C J

    1997-01-01

    Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach t...

  11. Periodontal vaccine

    OpenAIRE

    Ranjan Malhotra; Anoop Kapoor; Vishakha Grover; Aaswin Kaur Tuli

    2011-01-01

    Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of pe...

  12. Funded Projects | Division of Cancer Prevention

    Science.gov (United States)

    Breast Cancer (vaccines)Plac1 vaccine for breast cancer preventionEfficacy of a multi-antigen vaccine in the prevention of methynitrosourea-induced mammary cancers (ER+) in female Sprague-Dawley rats Breast Cancer (small molecules and biomarkers)Chemopreventive effects in both standard chow diets and high-fat diets of known positive- and negative-chemopreventive agents employing both high-risk (but histologically normal) mammary epithelium and mammary cancers including correlative biomarkers | Breast Cancer (vaccines) Cervical Cancer (small molecule) Colon Cancer (small molecules, vaccine, biomarker) Lung Cancer (small molecules, vaccine, biomarker, vaccine) Pancreatic Cancer (small molecule) Prostate Cancer (small molecule) Oral Cancer (small molecule) Skin Cancer (small molecule)

  13. DNA vaccines against influenza.

    Science.gov (United States)

    Stachyra, Anna; Góra-Sochacka, Anna; Sirko, Agnieszka

    2014-01-01

    Genetic vaccine technology has been considerably developed within the last two decades. This cost effective and promising strategy can be applied for therapy of cancers and for curing allergy, chronic and infectious diseases, such as a seasonal and pandemic influenza. Despite numerous advantages, several limitations of this technology reduce its performance and can retard its commercial exploitation in humans and its veterinary applications. Inefficient delivery of the DNA vaccine into cells of immunized individuals results in low intracellular supply of suitable expression cassettes encoding an antigen, in its low expression level and, in turn, in reduced immune responses against the antigen. Improvement of DNA delivery into the host cells might significantly increase effectiveness of the DNA vaccine. A vast array of innovative methods and various experimental strategies have been applied in order to enhance the effectiveness of DNA vaccines. They include various strategies improving DNA delivery as well as expression and immunogenic potential of the proteins encoded by the DNA vaccines. Researchers focusing on DNA vaccines against influenza have applied many of these strategies. Recent examples of the most successful modern approaches are discussed in this review.

  14. HPV Vaccine

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness HPV Vaccine KidsHealth > For Teens > HPV Vaccine Print A A A What's in this article? ... 11 or 12 through age 21 If needed, kids can get the vaccine starting at age 9. continue How Does the ...

  15. 宫颈癌防治用人乳头瘤病毒疫苗的研究进展%Research progress of human papillomavirus vaccine in the prevention and treatment of cervical cancer

    Institute of Scientific and Technical Information of China (English)

    夏和霞; 张炜

    2016-01-01

    Human papillomavirus (HPV) is closely related to the development of cervical cancer. The role of HPV vaccine in the prevention and treatment of cervical diseases caused by HPV infection is gradually taken into account. This review summarizes the recent research progress of preventive and therapeutic HPV vaccines in the prevention and treatment of cervical cancer. Quadrivalent HPV (HPV6/11/16/18) vaccine Gardasil, bivalent HPV (HPV16/18) vaccine Cervarix, and a new nine-valent HPV (HPV6/11/16/18/31/33/45/52/58) vaccine Gardasil 9 have been listed and applied in clinic among the preventive vaccines. However, therapeutic HPV vaccines are still in the research stage and more experiments are needed to improve the immunogenicity and safety for clinical trials in humankind.%高危型人乳头瘤病毒(human papillomavirus, HPV)感染与宫颈癌的发生、发展关系密切。HPV疫苗在HPV感染所致宫颈疾病防治中的作用逐渐受到重视。本文介绍宫颈癌防治用预防性和治疗性HPV疫苗的研究进展。预防性HPV疫苗中的四价HPV(HPV6/11/16/18)疫苗Gardasil、二价HPV(HPV16/18)疫苗Cervarix和九价HPV (HPV6/11/16/18/31/33/45/52/58)疫苗Gardasil 9已获准上市并用于临床。治疗性HPV疫苗均尚处于研究阶段,且免疫原性与安全性仍有待提高。

  16. A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

    Science.gov (United States)

    Kakimi, Kazuhiro; Isobe, Midori; Uenaka, Akiko; Wada, Hisashi; Sato, Eiichi; Doki, Yuichiro; Nakajima, Jun; Seto, Yasuyuki; Yamatsuji, Tomoki; Naomoto, Yoshio; Shiraishi, Kenshiro; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Oka, Mikio; Pan, Linda; Hoffman, Eric W; Old, Lloyd J; Nakayama, Eiichi

    2011-12-15

    We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.

  17. Retrospective Comparative Study of the Effects of Dendritic Cell Vaccine and Cytokine-Induced Killer Cell Immunotherapy with that of Chemotherapy Alone and in Combination for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jingxiu Niu

    2014-01-01

    Full Text Available Purpose. This retrospective study determined the delayed-type hypersensitivity (DTH skin test and safety of dendritic cell (DC vaccine and cytokine-induced killer (CIK cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC patients. Methods. DTH and safety of the immunotherapy were recorded. The overall survival (OS and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates. Results. Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST (198.00 days was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days (P=0.02. For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy (P=0.41. MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone (P=0.41. Conclusions. DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS.

  18. DNA vaccines

    Science.gov (United States)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  19. FLU VACCINATION

    CERN Multimedia

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  20. Periodontal vaccine

    Directory of Open Access Journals (Sweden)

    Ranjan Malhotra

    2011-01-01

    Full Text Available Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of periodontal vaccine would not only prevent and modulate periodontal disease, but also enhance the quality of life of people for whom periodontal treatment cannot be easily obtained. The aim of the research should be development of a multispecies vaccine targeting the four prime periodontal pathogens, viz. Porphyromonas gingivalis, T. forsythus, T. denticola and A. comitans. Success is still elusive in case of periodontal vaccine due to the complex etiopathogenesis of the disease.

  1. Vaccination of prostate cancer patients with modified vaccinia ankara delivering the tumor antigen 5T4 (TroVax): a phase 2 trial.

    Science.gov (United States)

    Amato, Robert J; Drury, Noel; Naylor, Stuart; Jac, Jaroslaw; Saxena, Somya; Cao, Amy; Hernandez-McClain, Joan; Harrop, Richard

    2008-01-01

    The attenuated vaccinia virus, modified vaccinia Ankara, has been engineered to deliver the tumor antigen 5T4 (TroVax). TroVax has been evaluated in an open-label phase 2 trial in hormone refractory prostate cancer patients in which the vaccine was administered either alone or in combination with granulocyte macrophage-colony stimulating factor (GM-CSF). The comparative safety and immunologic and clinical efficacy of TroVax alone or in combination with GM-CSF was determined. Twenty-seven patients with metastatic hormone refractory prostate cancer were treated with TroVax alone (n=14) or TroVax+GM-CSF (n=13). 5T4-specific cellular and humoral responses were monitored throughout the study. Clinical responses were assessed by quantifying prostate-specific antigen concentrations and measuring changes in tumor burden by computer-assisted tomography scan. TroVax was well tolerated in all patients with no serious adverse events attributed to vaccination. Of 24 immunologically evaluable patients, all mounted 5T4-specific antibody responses. Periods of disease stabilization from 2 to >10 months were observed. Time to progression was significantly greater in patients who mounted 5T4-specific cellular responses compared with those who did not (5.6 vs. 2.3 mo, respectively). There were no objective clinical responses seen in this study. In this study, the combination of GM-CSF with TroVax showed similar clinical and immunologic responses to TroVax alone. The high frequency of 5T4-specific immune responses and relationship with enhanced time to progression is encouraging and warrants further investigation.

  2. A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer.

    Science.gov (United States)

    Noguchi, Masanori; Kakuma, Tatsuyuki; Uemura, Hirotsugu; Nasu, Yasutomo; Kumon, Hiromi; Hirao, Yasuhiko; Moriya, Fukuko; Suekane, Shigetaka; Matsuoka, Kei; Komatsu, Nobukazu; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo

    2010-07-01

    Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

  3. Recent advances towards the clinical application of DNA vaccines.

    Science.gov (United States)

    Bins, A D; van den Berg, J H; Oosterhuis, K; Haanen, J B A G

    2013-04-01

    DNA vaccination is an attractive method for therapeutic vaccination against intracellular pathogens and cancer. This review provides an introduction into the DNA vaccination field and discusses the pre-clinical successes and most interesting clinical achievements thus far. Furthermore, general attributes, mechanism of action and safety of DNA vaccination will be discussed. Since clinical results with DNA vaccination so far show room for improvement, possibilities to improve the delivery and immunogenicity of DNA vaccines are reviewed. In the coming years, these new developments should show whether DNA vaccination is able to induce clinically relevant responses in patients.

  4. Overview of Current Humman Papilloma Virus (HPV Vaccination

    Directory of Open Access Journals (Sweden)

    Cumhur Artuk

    2013-06-01

    Full Text Available Persistent viral infection with high-risk human papillomavirus (HPV genotypes causes virtually all cancer of the cervix. The same HPV genotypes (“types” also cause cases of anal cancer. Cervical cancer is the third most frequent cancer in women worldwide after breast and colorectal cancers. It ranks fourth of women’s cancers according to the mortality ratio. Two vaccines have been developed against HPV infection; one is a quadrivalent vaccine (Gardasil™ and the other is a bivalent vaccine (Cervarix™. This topic will cover issues related to HPV infections, routine HPV immunization recommendations, vaccination in special patient populations, the cost-effectiveness of HPV vaccination, and vaccine safety. [TAF Prev Med Bull 2013; 12(3.000: 327-334

  5. Novel Method Of Preparing Vaccines | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    This invention from the NCI Cancer and Inflammation Program describes methods to prepare vaccines for the treatment of human immunodeficiency virus (HIV) infections. The National Cancer Institute's Cancer and Inflammation Program seeks parties interested in licensing or collaborative research to further develop, evaluate, or commercialize novel methods of preparing vaccines.

  6. A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer.

    Science.gov (United States)

    Klyushnenkova, Elena N; Kouiavskaia, Diana V; Parkins, Christopher J; Caposio, Patrizia; Botto, Sara; Alexander, Richard B; Jarvis, Michael A

    2012-06-01

    Cytomegalovirus (CMV) is a highly immunogenic virus that results in a persistent, life-long infection in the host typically with no ill effects. Certain unique features of CMV, including its capacity to actively replicate in the presence of strong host CMV-specific immunity, may give CMV an advantage compared with other virus-based vaccine delivery platforms. In the present study, we tested the utility of mouse CMV (mCMV)-based vaccines expressing human prostate-specific antigen (PSA) for prostate cancer immunotherapy in double-transgenic mice expressing PSA and HLA-DRB1*1501 (DR2bxPSA F1 mice). We assessed the capacity of 2 mCMV-based vectors to induce PSA-specific CD8 T-cell responses and affect the growth of PSA-expressing Transgenic Adenocarcinoma of the Mouse Prostate tumors (TRAMP-PSA). In the absence of tumor challenge, immunization with mCMV vectors expressing either a H2-D(b)-restricted epitope PSA(65-73) (mCMV/PSA(65-73)) or the full-length gene for PSA (mCMV/PSA(FL)) induced comparable levels of CD8 T-cell responses that increased (inflated) with time. Upon challenge with TRAMP-PSA tumor cells, animals immunized with mCMV/PSA(65-73) had delay of tumor growth and increased PSA-specific CD8 T-cell responses, whereas animals immunized with mCMV/PSA(FL) showed progressive tumor growth and no increase in number of splenic PSA(65-73)-specific T cells. The data show that a prototype CMV-based prostate cancer vaccine can induce an effective antitumor immune response in a "humanized" double-transgenic mouse model. The observation that mCMV/PSA(FL) is not effective against TRAMP-PSA is consistent with our previous findings that HLA-DRB1*1501-restricted immune responses to PSA are associated with suppression of effective CD8 T-cell responses to TRAMP-PSA tumors.

  7. A New Decade of Vaccines

    LENUS (Irish Health Repository)

    Murphy, JFA

    2011-09-01

    The call for a new decade of vaccines was made in December 2010. The aims are to secure the further discovery, development and delivery of vaccination. The first challenge is the acquisition of funds for the research and development of 20 new vaccines1. The Gates Foundation has pledged $10 billion for this venture. The other major players are WHO, UNICEF and the US National Institute of Allergy and Infectious Diseases. The top priorities are TB, AIDS and Malaria. It is hoped that a Malaria vaccine will available in 3 years. The ambitious target of saving the lives of over 7 million children has been set. The programme must also address the need for vaccines in insulin dependent diabetes, cancers and degenerative diseases2.

  8. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer

    Science.gov (United States)

    2010-07-31

    stimulate anti-tumor immunity . We demonstrated that DC/breast carcinoma fusions strongly express costimulatory, adhesion, and maturation markers as...can initiate the study. Our correspondence is summarized below: 1. Request for further information from DOD issued 3.4.09 2. Reponses to...days 3 and 5. Measures of tumor specific cellular and humoral immunity will be obtained at serial time points following vaccination. Time to disease

  9. Progression of the Clinical Application of HPV Vaccine in Cervical Cancer Prevention%HPV疫苗预防子宫颈癌的临床应用进展及思考

    Institute of Scientific and Technical Information of China (English)

    朱巧玲; 吴宜林

    2012-01-01

    子宫颈癌是引起女性死亡的第二大癌症.研究证实人乳头瘤病毒(HPV)感染与子宫颈癌有着十分密切的关系.近年来,HPV疫苗在预防和治疗子宫颈癌方面备受关注,多种新型预防性HPV疫苗已在部分国家上市.但是HPV疫苗的研制、使用、推广仍面临许多难题,有待广大医疗工作者共同思考和解决.%Cervical cancer is the second\\cause of cancer death in women, many studies confirm that human papillomavirus (HPV) infection and cervical cancer has, a very close relationship. In recent years, HPV vaccines get much attention in the fields of cervical cancer prevention and treatment, a variety of new preventive HPV vaccines have been used in some countries. But the development, use and promotion of HPV vaccine are still facing many challenges, so we need think about that and solve the problems together.

  10. A Phase I Trial of Pox PSA vaccines (PROSTVAC®-VF with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™ in Patients with Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Lattime E

    2006-01-01

    Full Text Available Abstract Purpose Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM™ to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM. Methods In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l08 pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V followed by 1 × 109 pfu of the booster recombinant fowlpox virus (PROSTVAC-F both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79. The mean PSA at baseline was 434 (range 9 – 1424. Results There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients. Conclusion This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.

  11. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  12. FLU VACCINATION

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  13. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  14. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  15. Cost-Utility Analysis of Human Papillomavirus Vaccination and Cervical Screening on Cervical Cancer Patient in Indonesia

    NARCIS (Netherlands)

    Setiawan, Didik; Dolk, Franklin Christiaan; Suwantika, Auliya A.; Westra, Tjalke Arend; WIlschut, Jan C.; Postma, Maarten Jacobus

    2016-01-01

    Background: Although cervical cancer is a preventable disease, the clinical and economic burdens of cervical cancer are still substantial issues in Indonesia. Objectives: The main purpose of this study was to model the costs, clinical benefits, and cost-utility of both visual inspection with acetic

  16. Leptospirosis vaccines

    OpenAIRE

    Jin Li; Wang Zhijun; Węgrzyn Alicja

    2007-01-01

    Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the...

  17. A convenient cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid using gene gun technology after priming with irradiated carcinoma cells.

    Science.gov (United States)

    Nishitani, Masa-aki; Sakai, Tohru; Ishii, Kazunari; Zhang, Manxin; Nakano, Yoko; Nitta, Yoshio; Miyazaki, Jun-ichi; Kanayama, Hiro-omi; Kagawa, Susumu; Himeno, Kunisuke

    2002-02-01

    We studied interleukin (IL)-12 gene therapy using a gene gun as a new autologous vaccination strategy for cancer. In the first experiment, BALB/c mice were inoculated with syngeneic murine renal cancer cells (Renca) intradermally in the abdomen. This was followed by an injection of IL-12 expression plasmid using the gene gun. About 40% of the mice exhibited rejection of the tumor after the treatment and these mice also acquired immunological resistance against a secondary challenge with Renca cells. Based on these results, we examined whether antitumor activity can be potentiated when mice undergo combination treatment with intradermal inoculation of irradiated Renca cells and transfection with IL-12 gene. Inoculation of irradiated Renca cells alone was partially effective in inducing antitumor immunity, whereas the combined treatment remarkably intensified this effect. Moreover, this combined treatment inhibited tumor establishment and enhanced survival of the mice with tumor infiltration by CD4(+) and CD8(+) T cells, even when the treatment was started after tumor-implantation at a distant site. This antitumor effect was antigen specific and we confirmed the induction of antitumor cytotoxic T cells by this treatment. These results show that local cutaneous transfer of IL-12 expression plasmid using gene gun technology enhances systemic and specific antitumor immunity primed by irradiated tumor cells.

  18. Knowledge and Awareness of HPV Vaccine and Acceptability to Vaccinate in Sub-Saharan Africa: A Systematic Review

    Science.gov (United States)

    Perlman, Stacey; Wamai, Richard G.; Bain, Paul A.; Welty, Thomas; Welty, Edith; Ogembo, Javier Gordon

    2014-01-01

    Objectives We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA) countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination. Methods We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3) vaccine coverage in SSA countries from 1990–2011 were extracted from the World Health Organization database. Findings The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1) the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2) achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above. Conclusion There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, (adolescents, parents and healthcare professionals), to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to qualify for GAVI

  19. Knowledge and awareness of HPV vaccine and acceptability to vaccinate in sub-Saharan Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Stacey Perlman

    Full Text Available OBJECTIVES: We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination. METHODS: We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3 vaccine coverage in SSA countries from 1990-2011 were extracted from the World Health Organization database. FINDINGS: The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1 the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2 achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above. CONCLUSION: There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, (adolescents, parents and healthcare professionals, to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to

  20. HPV virus and youth vaccination

    Directory of Open Access Journals (Sweden)

    Ifanti Ε.

    2013-04-01

    Full Text Available Background: Human Papilloma Virus (HPV is considered the major cause of cervical cancer. Its primary prevention is nowadays possible with the vaccination against HPV. Aim: It was to investigate the vaccination level of the children of Greek and Immigrants, aged 12-18 years old, regarding the vaccination against HPV. Results: None of the boys and the children of immigrants had ever been vaccinated against HPV. 5.3% of the Junior High School and High School females were fully vaccinated against the virus. Material and method: The sample of the study consisted of Greek and immigrants High Schools and Junior High Schools’ pupils aged 12-18 years old. Children’s personal Health Cards were used to evaluate the adequacy of vaccine doses. χ2 was used for comparisons. Statistics was processed with SPSS 17.0. Conclusion: The vaccination coverage of adolescents against HPV is at very low levels. There is an emergency of organizing the appropriate vaccination programs, especially in Greek provincial areas.

  1. Phenotypic and functional characterization of clinical grade dendritic cells generated from patients with advanced breast cancer for therapeutic vaccination

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Thorn, M; Gad, M;

    2005-01-01

    Dendritic cells (DC) are promising candidates for cancer immunotherapy. However, it is not known whether in vitro-generated monocyte-derived DC from cancer patients are altered compared with DC from healthy donors. In a clinical phase I/II study, monocyte-derived DC were generated in vitro...... utilizing granulocyte macrophage colony-stimulating factor and rh-interleukin-4 (IL-4) and used for cancer immunotherapy. In this study, we tested the effect of various maturation cocktails and performed a comparative evaluation of the DC phenotype and functional characteristics. Polyriboinosinic...

  2. Perspectivas para el desarrollo de vacunas e inmunoterapia contra cáncer cervicouterino Perspectives for vaccines and immunotherapy against cervical cancer

    Directory of Open Access Journals (Sweden)

    LILIANA GUZMÁN-ROJAS

    1998-01-01

    Full Text Available El cáncer cervicouterino representa un grave problema de salud pública, debido a la asociación de la neoplasia con el virus del papiloma humano; actualmente se realizan estudios usando estrategias dirigidas a combatir este patógeno, mediante vacunas, que podrían ser de gran utilidad para el control de la progresión de la enfermedad. El estudio tanto de la inmunología humoral como celular ha servido para el desarrollo de vacunas. Así, la utilización de partículas virales sintéticas para el estudio de anticuerpos neutralizantes y el uso de proteínas tempranas virales, entre otras, para la inducción de inmunidad mediada por células, han sido la pauta para realizar estudios que dirijan la respuesta inmune para prevenir la infección celular tanto hacia células infectadas no transformadas como hacia células transformadas viralmente con resultados favorables.Cervical cancer represents a severe public health problem and has been associated to the presence of human papillomavirus. Strategies are presently being tested which target the virus to attempt to control disease progress. Studies on the humoral and cell-mediated immunity of the papillomavirus infection have been useful in the development of a vaccine. Synthetic virus-like particles have been validated as vaccine against several animal papillomaviruses and used to map the seroepidemiology of the human papillomavirus infection, and define neutralizing antibodies. Induction of cell-mediated immunity to HPV early proteins is bound to become a therapeutic approach to HPV infections. Recent advances have centered on directing the immune response to prevent infection, to virus-infected cells and to virally transformed cells, with favourable results.

  3. Fusion of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer. Addendum

    Science.gov (United States)

    2011-08-01

    patients. This brief report details the characterization of tumor cells and dendritic cells generated from patient BV01 with metastatic breast cancer following isolation from pleural effusions and leukapheresis, respectively.

  4. Children, the Flu, and the Flu Vaccine

    Science.gov (United States)

    ... Cancer Parents Children, the Flu, and the Flu Vaccine Children and Flu Antiviral Drugs Caregivers of Young Children ... of Developing Flu–Related Complications . There are special vaccination instructions for children aged 6 months through 8 years of age ...

  5. Advance in clinical research of non-small cell lung cancer vaccines%非小细胞肺癌疫苗治疗的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    杨露璐; 吴一龙

    2012-01-01

    The therapeutic cancer vaccines have low toxicity and well tolerance. However, many clinical studies of vaccines for NSCLC have not made significant progress. The major difficulties in the development of therapeutic cancer vaccines include the lack of tumor specific antigen, the tumor escape mechanisms from host immune surveillance and immune tolerance. In recent years, new insights in the interaction between tumors and the immune system, the better identification of antigenic targets, the addition of immunoadjuvants and the production of more efficient delivery systems have resulted in more sophisticated vaccines, such as antigen-specific vaccines targeting melanoma-associated antigen-A3 , mucin 1 and EGF, and whole-cell vaccines such as belagenpumatucel-L. These vaccines have shown promising results in phase II clinical trials, and need to be evaluated in Phase II clinical trials.%非小细胞肺癌(non-small cell lung cancer,NSCLC)的疫苗治疗具有不良反应小、耐受性好的特点,但众多的临床研究并未取得突破性的进展.影响疫苗治疗肺癌的主要困难包括由于肿瘤免疫原性弱而缺乏肿瘤特异性抗原以及宿主免疫监视下的肿瘤免疫逃逸和免疫耐受.近几年来,随着人们对肿瘤和免疫系统关系的进一步认识,特异性肿瘤抗原的发现及免疫佐剂和载体的发展,疫苗治疗NSCLC已经取得了显著的进展,如melanoma-associated antigen-A3疫苗、针对mucin 1抗原的疫苗、EGF疫苗等抗原特异性疫苗以及将TGF-β2转染NSCLC细胞株制成的全细胞疫苗Belagenpumatucel-L等.多个Ⅱ期临床研究已经证实了它们在NSCLC中的疗效,相应多中心的Ⅲ期临床研究正在进行中.

  6. Selecting Viruses for the Seasonal Influenza Vaccine

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  7. Seasonal Flu Vaccine Safety and Pregnant Women

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  8. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

    Science.gov (United States)

    Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

    1999-10-01

    In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

  9. Potential benefits of second-generation human papillomavirus vaccines.

    Directory of Open Access Journals (Sweden)

    Sorapop Kiatpongsan

    Full Text Available BACKGROUND: Current prophylactic vaccines against human papillomavirus (HPV target two oncogenic types (16 and 18 that contribute to 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to expand protection to five additional oncogenic types (31, 33, 45, 52 and 58. METHODS: A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda was used to estimate reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the independent and joint impact of uncertain factors (i.e., distribution of HPV types, co-infection with multiple HPV types, and unidentifiable HPV types in cancer and vaccine properties (i.e., cross-protection against non-targeted HPV types, compared against currently-available vaccines. RESULTS: Assuming complete uptake of the second-generation vaccine, reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda, representing an absolute increase in cervical cancer reduction of 26.1% in Kenya and 17.9% in Uganda, compared with complete uptake of current vaccines. The range of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda, depending on assumptions of cancers attributable to multiple HPV infections and unidentifiable HPV types. These effects were blunted in both countries when assuming vaccine cross-protection with both the current and second-generation vaccines. CONCLUSION: Second-generation HPV vaccines that protect against additional oncogenic HPV types have the potential to improve cervical cancer prevention. Co-infection with multiple HPV infections and unidentifiable HPV types can influence vaccine effectiveness, but the magnitude of effect may be moderated by vaccine cross-protective effects. These benefits must be weighed against the cost of the vaccines in future

  10. Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma.

    Science.gov (United States)

    Iwahashi, Makoto; Katsuda, Masahiro; Nakamori, Mikihito; Nakamura, Masaki; Naka, Teiji; Ojima, Toshiyasu; Iida, Takeshi; Yamaue, Hiroki

    2010-12-01

    Potent helper action is necessary for peptide-based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA-A*2402 using epitope peptides derived from novel cancer-testis antigens, LY6K and TTK, in combination with CpG-7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen-specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28-day treatment cycle with peptide LY6K-177, peptide TTK-567, and CpG-7909 (level-1; 0, level-2; 0.02, level-3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K-specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level-2/3 showed potent LY6K-specific T cell responses. In contrast, only two patients in level-2/3 showed TTK-567-specific T cell responses. The frequency of LY6K-177 or TTK-567-specific CD8+ T cells increased in patients in level-2/3 (with CpG). The vaccination with peptides and CpG-7909 increased and activated both plasmacytoid dendritic cells and natural killer cells, and increased the serum level of α-interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level-1, and four of six patients in level-2/3 showed stable disease (SD). In conclusion, vaccination with LY6K-177 and TTK-567 in combination with CpG-7909 successfully elicited antigen-specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials.

  11. Risk in vaccine research and development quantified.

    Directory of Open Access Journals (Sweden)

    Esther S Pronker

    Full Text Available To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates have been published for new chemical entities (NCE, little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines.

  12. Human papillomavirus prevalence and type-distribution, cervical cancer screening practices and current status of vaccination implementation in Russian Federation, the Western countries of the former Soviet Union, Caucasus region and Central Asia.

    Science.gov (United States)

    Rogovskaya, Svetlana I; Shabalova, Irina P; Mikheeva, Irina V; Minkina, Galina N; Podzolkova, Nataly M; Shipulina, Olga Y; Sultanov, Said N; Kosenko, Iren A; Brotons, Maria; Buttmann, Nina; Dartell, Myassa; Arbyn, Marc; Syrjänen, Stina; Poljak, Mario

    2013-12-31

    Limited data are available on the burden of human papillomavirus (HPV) and its associated diseases in the Russian Federation, the Western Countries of the former Soviet Union (Belarus, Republic of Moldova, Ukraine), the Caucasus region and Central Asia (Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan). Both the incidence and mortality rate of cervical cancer are higher in these countries than in most Western European countries. In this article, we review available data on HPV prevalence and type distribution in women with normal cytology, women from the general population, cervical precancerous lesions and cervical cancer, as well as data on national policies of cervical cancer screening and HPV vaccination initiatives in these countries. Based on scarce data from the 12 countries, the high-risk HPV (hrHPV) prevalence among 5226 women with normal cytology ranged from 0.0% to 48.4%. In women with low-grade cervical lesions, the hrHPV prevalence among 1062 women varied from 29.2% to 100%. HrHPV infection in 565 women with high-grade cervical lesions ranged from 77.2% to 100% and in 464 invasive cervical cancer samples from 89.8% to 100%. HPV16 was the most commonly detected hrHPV genotype in all categories. As the HPV genotype distribution in cervical diseases seems to be similar to that found in Western Europe the implementation of HPV testing in screening programs might be beneficial. Opportunistic screening programs, the lack of efficient call-recall systems, low coverage, and the absence of quality assured cytology with centralized screening registry are major reasons for low success rates of cervical cancer programs in many of the countries. Finally, HPV vaccination is currently not widely implemented in most of the twelve countries mainly due to pricing, availability, and limited awareness among public and health care providers. Country-specific research, organized nationwide screening programs, registries and well

  13. Immune modulations during chemoimmunotherapy & novel vaccine strategies - In metastatic melanoma and non small-cell lung cancer

    DEFF Research Database (Denmark)

    Iversen, Trine Zeeberg

    2013-01-01

    This thesis describes the treatment of metastatic melanoma (MM) and non small-cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the first part of the thesis was to assess how treatment with Temozolomide (TMZ) chemotherapy affects the immune system in patients with metast......This thesis describes the treatment of metastatic melanoma (MM) and non small-cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the first part of the thesis was to assess how treatment with Temozolomide (TMZ) chemotherapy affects the immune system in patients...

  14. How does HPV vaccination status relate to risk perceptions and intention to participate in cervical screening?

    DEFF Research Database (Denmark)

    Hestbech, Mie Sara; Gyrd-Hansen, Dorte; Kragstrup, Jakob;

    2016-01-01

    Background: Women in several countries will soon be covered by two preventive programmes targeting cervical cancer: HPV vaccination and cervical screening. The HPV vaccines are expected to prevent approximately 70 % of cervical cancers. It has been speculated, that HPV vaccinated women...... will not attend screening because they falsely think that the vaccine has eliminated their cervical cancer risk. The aim of this study was to investigate the association between HPV vaccination status and perceptions of cervical cancer risk; perceptions of vaccine effect; and intention to participate in cervical...... and intentions to participate in cervical screening. Main outcomes were: perceived lifetime-risk of cervical cancer; perceived HPV vaccine effect; and intention to participate in cervical screening. Results: HPV vaccinated women more often than unvaccinated women intended to participate in screening: adjusted...

  15. Antitumor effects of human interferon-alpha 2b secreted by recombinant bacillus Calmette-Guérin vaccine on bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Guo-qing DING; Yan-lan YU; Zhou-jun SHEN; Xie-lai ZHOU; Shan-wen CHEN; Guo-dong LIAO; Yue ZHANG

    2012-01-01

    Objective:Our objective was to construct a recombinant bacillus Calmette-Guénn vaccine (rBCG) that secretes human interferon-alpha 2b (IFNα-2b) and to study its immunogenicity and in vitro antitumor activity against human bladder cancer cell lines T24 and T5637.Methods:The signal sequence BCG Ag85B and the gene IFNα-2b were amplified from the genome of BCG and human peripheral blood,respectively,by polymerase chain reaction (PCR).The two genes were cloned in Escherichia coli-BCG shuttle-vector pMV261 to obtain a new recombinant plasmid pMV261-Ag85B-IFNα-2b.BCG was transformed with the recombinant plasmid by electroporation and designated rBCG-IFNα-2b.Mononuclear cells were isolated from human peripheral blood (PBMCs) and stimulated with rBCG-IFNα-2b or wild type BCG for 3 d,and then cultured with human bladder cancer cell lines T24 and T5637.Their cytotoxicities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Results:BCG was successfully transformed with the recombinant plasmid pMV261-Ag85B-IFNα-2b by electroporation and the recombinant BCG (rBCG-IFNα-2b) was capable of synthesizing and secreting cytokine IFNα-2b.PBMC proliferation was enhanced significantly by rBCG-IFNα-2b,and the cytotoxicity of PBMCs stimulated by rBCG-IFNα-2b to T24 and T5627 was significantly stronger in comparison to wild type BCG.Conclusions:A recombinant BCG,secreting human IFNα-2b (rBCG-IFNα-2b),was constructed successfully and was superior to control wild type BCG in inducing immune responses and enhancing cytotoxicity to human bladder cancer cell lines T24 and T5637.This suggests that rBCG-IFNα-2b could be a promising agent for bladder cancer patients in terms of possible reductions in both clinical dosage and side effects of BCG immunotherapy.d enhancng c

  16. 乳腺癌疫苗中肿瘤抗原的鉴定%Identification of Tumor Antigen in the Breast Cancer Vaccine

    Institute of Scientific and Technical Information of China (English)

    刘安军; 方菁菁; 马姗婕

    2013-01-01

    The tumor antigen in the breast cancer vaccine which activated the anti-tumor immunity response was determined according to the antigen-specific antibodies existent in the serum of the immunized mice by immunoproteomics analysis.The results showed that the antibody titer of immunized mice serum was over 6400 and the high antibody titer suggested that the humoral immunity on anticancer was strengthened.SDS-PAGE and western-blot analysis showed that the protein extracted from Ca761 cells treated with cartilage polysaccharide was bonded with the immune serum at an estimated molecular mass of 50 kDa.2D-PAGE and western-blot analysis showed that the tumor antigens activated anti-tumor immune response were acidic protein at 50 kDa.By MALDI-TOF-MS,the reactive protein was identified as α-tubulin.In summary,structure and expression of tumor antigen (α-tubulin) in Ca761 cells was modified with the cartilage polysaccharide treatment,therefore,the anti-tumor immunity of mice was activated by the tumor vaccine so that the mice immunized with the tumor vaccine could prevent from invasion of tumor cells.The immunogenic of α-tubulin was strengthened after the treatment with cartilage polysaccharide,which could be developed as a new vaccine.%鉴定乳腺癌疫苗中激活小鼠抗肿瘤免疫反应的肿瘤抗原.利用蛋白质组学方法根据免疫小鼠血清中存在的特异性抗体寻找肿瘤疫苗所含的肿瘤抗原.结果表明,肿瘤疫苗免疫小鼠的抗体效价大于6400,证明免疫小鼠血清中抗体含量高,且其抗肿瘤体液免疫得到增强;SDS-PAGE结合免疫印迹结果证明,软骨多糖作用后的Ca761细胞,与免疫血清在50kDa左右出现了特异性结合的蛋白条带;二维电泳结合免疫印迹确定了激活免疫反应的肿瘤抗原为50 kDa酸性蛋白,经质谱技术鉴定,该肿瘤抗原为α-tubulin.综上所述,Ca761细胞中的肿瘤抗原α-tubulin经软骨多糖作用后,其结构及表达量发生了变化,该

  17. HPV vaccination to prevent oropharyngeal carcinoma: What can be learned from anogenital vaccination programs?

    Science.gov (United States)

    Takes, Robert P; Wierzbicka, Małgorzata; D'Souza, Gypsyamber; Jackowska, Joanna; Silver, Carl E; Rodrigo, Juan P; Dikkers, Frederik G; Olsen, Kerry D; Rinaldo, Alessandra; Brakenhoff, Ruud H; Ferlito, Alfio

    2015-12-01

    Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was conducted and available vaccines and vaccination strategies in HNSCC and OPC are discussed. Prophylactic vaccination is known to be effective for prevention of anogenital HPV infection and precursor lesions in the cervix and anus. While the value of vaccination for prevention of OPC and possibly as an adjuvant treatment is still an open question, evidence to date supports the possibility that HPV vaccination may prove to be effective in reducing the incidence of this malignancy.

  18. Human papilloma virus vaccines: Current scenario

    Directory of Open Access Journals (Sweden)

    Deepika Pandhi

    2011-01-01

    Full Text Available Genital human papillomavirus (HPV infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9-13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40-60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil® is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9-26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9-26 years of age for the prevention of genital warts. Cervarix™ is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10-25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines.

  19. Alphavirus-based vaccines.

    Science.gov (United States)

    Lundstrom, Kenneth

    2014-06-16

    Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.

  20. Alphavirus-Based Vaccines

    Directory of Open Access Journals (Sweden)

    Kenneth Lundstrom

    2014-06-01

    Full Text Available Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.

  1. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Chunfeng Qu

    2014-12-01

    Full Text Available BACKGROUND: Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV infections. Its long-term protective efficacy on primary liver cancer (PLC and other liver diseases has not been fully examined. METHODS AND FINDINGS: The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8% participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2% in the vaccination group and 3,898 (11.3% in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770 and 50.7% (17,204 in the vaccination group and 36.3% (12,184 and 58.6% (17,395 in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%, 70% (95% CI 15%-89%, and 69% (95% CI 34%-85%, respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%, substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%. Receiving a booster at age 10

  2. Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer.

    Science.gov (United States)

    2013-07-01

    specific CD4+ helper T cell responses in cancer patients. Blood, 106:1008- 1011 , 2005. (2) Bell D, Chomarat P, Broyles D, Netto G, Harb GM, Lebecque S...regulatory t cell proliferation. J Exp Med, 2005, 202: 919- 929 . (4) Rabinowich H, Suminami Y, Reichert TE, Crowley-Nowick P, Bell M, Edwards R

  3. LECTINPred: web Server that Uses Complex Networks of Protein Structure for Prediction of Lectins with Potential Use as Cancer Biomarkers or in Parasite Vaccine Design.

    Science.gov (United States)

    Munteanu, Cristian R; Pedreira, Nieves; Dorado, Julián; Pazos, Alejandro; Pérez-Montoto, Lázaro G; Ubeira, Florencio M; González-Díaz, Humberto

    2014-04-01

    Lectins (Ls) play an important role in many diseases such as different types of cancer, parasitic infections and other diseases. Interestingly, the Protein Data Bank (PDB) contains +3000 protein 3D structures with unknown function. Thus, we can in principle, discover new Ls mining non-annotated structures from PDB or other sources. However, there are no general models to predict new biologically relevant Ls based on 3D chemical structures. We used the MARCH-INSIDE software to calculate the Markov-Shannon 3D electrostatic entropy parameters for the complex networks of protein structure of 2200 different protein 3D structures, including 1200 Ls. We have performed a Linear Discriminant Analysis (LDA) using these parameters as inputs in order to seek a new Quantitative Structure-Activity Relationship (QSAR) model, which is able to discriminate 3D structure of Ls from other proteins. We implemented this predictor in the web server named LECTINPred, freely available at http://bio-aims.udc.es/LECTINPred.php. This web server showed the following goodness-of-fit statistics: Sensitivity=96.7 % (for Ls), Specificity=87.6 % (non-active proteins), and Accuracy=92.5 % (for all proteins), considering altogether both the training and external prediction series. In mode 2, users can carry out an automatic retrieval of protein structures from PDB. We illustrated the use of this server, in operation mode 1, performing a data mining of PDB. We predicted Ls scores for +2000 proteins with unknown function and selected the top-scored ones as possible lectins. In operation mode 2, LECTINPred can also upload 3D structural models generated with structure-prediction tools like LOMETS or PHYRE2. The new Ls are expected to be of relevance as cancer biomarkers or useful in parasite vaccine design.

  4. Introduction of human papillomavirus vaccination in Nordic countries

    DEFF Research Database (Denmark)

    Sander, Bente Braad; Rebolj, Matejka; Valentiner-Branth, Palle;

    2012-01-01

    Cervical screening has helped decrease the incidence of cervical cancer, but the disease remains a burden for women. Human Papillomavirus (HPV) vaccination is now a promising tool for control of cervical cancer. Nordic countries (Denmark, Finland, Greenland, Iceland, Norway and Sweden......) are relatively wealthy with predominantly publicly paid health care systems. The aim of this paper was to provide an update of the current status of introduction of HPV vaccine into the childhood vaccination programs in this region....

  5. HPV Vaccine Doesn't Eliminate Need for Pap Test

    Science.gov (United States)

    ... 2017 TUESDAY, Jan. 24, 2017 (HealthDay News) -- The HPV vaccine helps prevent cervical cancer but that doesn't mean women should forgo ... women have been vaccinated against the human papillomavirus (HPV) -- a virus that can cause cervical cancer -- they don't need to get screened every ...

  6. Dendritic cell-based cancer vaccines : Current status of global clinical trials%树突状细胞肿瘤疫苗:全球临床试验巡礼

    Institute of Scientific and Technical Information of China (English)

    陈虎; 唐晓义; 张斌

    2012-01-01

    自2011年度的诺贝尔生理学或医学奖获得者Ralph M.Steinman发现树突状细胞(dendritic cell,DC)及其在获得性免疫应答中的关键作用以来,全球范围的DC肿瘤疫苗研究持续进行了数十年,一系列临床试验正在进行或已经完成,目前已经有3种DC肿瘤疫苗获得了上市批准:Sipuleucel-T、CreaVax RCC和Hybricell,但基于DC的免疫治疗方法尚未成为肿瘤治疗的一种标准方法.为了让国内同行深入了解全球范围内开展DC肿瘤疫苗临床试验的现状,本文基于国际医学期刊编辑委员会认可的临床试验注册网站和PubMed网站数据库对全球DC肿瘤疫苗临床试验概况(地区和国家分布、涉及的肿瘤类型、开展年份和试验分期)作了介绍,重点对43项已经有论文发表的临床试验情况(受试者选择、DC培养方法、疫苗接种方案、疗效评估方法和试验结果)进行了总结,着重分析了当前DC肿瘤疫苗临床研究的发展趋势和存在问题,提出了加强DC肿瘤疫苗临床试验工作的若干建议:健全我国DC肿瘤疫苗临床试验相关的监管政策;密切关注国际“体内DC靶向”策略的新动向;抓紧建立DC培养方法、疫苗接种方案和疗效评估的标准;加强对DC肿瘤疫苗的质量监控;重视DC肿瘤疫苗的基础研究和临床试验注册;提高临床试验方案的质量;慎重选择受试患者和疗效评估时间点;治疗时应同步开展免疫监测等.抛砖引玉,以期引起国内同行的重视和讨论,并尽可能在将来的工作中加以研究和得到解决.%Dendritic cell ( DC)-based cancer vaccines have been studied for several decades and a line of clinical trials has been completed or in process since Ralph M. Steinman, a Nobel Prize winner in Physiology or Medicine 2011 , found DCs and their crucial role in adaptive immunity. Although three DC-based cancer vaccines (Sipuleucel-T, CreaVax RCC and Hybricel!) have been so far approved

  7. CDC Vital Signs: Cervical Cancer is Preventable

    Science.gov (United States)

    ... HPV vaccine can reduce risk of cervical cancer. HPV causes most cervical cancers. Only 1 in 3 girls and 1 in ... Signs – Cervical Cancer [PSA - 0:60 seconds] Cervical Cancer Preteen and Teen Vaccines Human Papillomavirus (HPV)-Associated Cancers What Should I Know About ...

  8. Vaccine Safety

    Science.gov (United States)

    ... Tweet Share Compartir Back to School: Vaccines for Preteens Learn about the safety of Tdap, Meningococcal, and ... file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file ...

  9. Typhoid Vaccine

    Science.gov (United States)

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, stomach ... a typhoid carrier. • Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot) • One dose provides ...

  10. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  11. Antipneumococcal vaccination

    Directory of Open Access Journals (Sweden)

    Gian Vincenzo Zuccotti

    2013-06-01

    Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  12. Your child's first vaccines

    Science.gov (United States)

    ... multi.html . CDC review information for Multi Pediatric Vaccines: Your Child's First Vaccines: What you need to know (VIS): ... baby. 2. Some children should not get certain vaccines Most children can safely get all of these vaccines. But ...

  13. Ear Infection and Vaccines

    Science.gov (United States)

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  14. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  15. Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose.

    Science.gov (United States)

    Lövgren, Tanja; Baumgaertner, Petra; Wieckowski, Sébastien; Devêvre, Estelle; Guillaume, Philippe; Luescher, Immanuel; Rufer, Nathalie; Speiser, Daniel E

    2012-06-01

    In mice, vaccination with high peptide doses generates higher frequencies of specific CD8+ T cells, but with lower avidity compared to vaccination with lower peptide doses. To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant. Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups. Also, CD8+ T cell differentiation and cytokine production ex vivo were similar in the two groups. Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo. In accordance, CD8+ T cell clones derived from low peptide dose-vaccinated patients showed significantly increased degranulation and stronger cytotoxicity. In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers. Furthermore, CD8+ T cell clones from low peptide dose-vaccinated patients bound CD8 binding-deficient tetramers more efficiently, suggesting that they may express higher affinity TCRs. We conclude that low peptide dose vaccination generated CD8+ T cell responses with stronger cytotoxicity and lower CD8 dependence.

  16. Revisiting the cost-effectiveness of universal HPV-vaccination in Denmark accounting for all potentially vaccine preventable HPV-related diseases in males and females

    DEFF Research Database (Denmark)

    Olsen, Jens; Jørgensen, Tine Rikke

    2015-01-01

    focussed on the quadrivalent vaccine which protects against HPV type 6, 11, 16 and 18, and the vaccine's protection against genital warts, cervical intraepithelial neoplasia, cervical cancer, anogenital cancer (anal, penile, vaginal and vulvar cancer) and head and neck cancer (oral cavity, oropharyngeal......, hypopharyngeal and laryngeal cancer) were included in the analyses. In general, the analysis was performed in two phases. First, an agent-based transmission model that described the HPV transmission without and with HPV vaccination was applied. Second, an analysis of the incremental costs and effects...... that would lead to a faster prevention of cancers, cancer precursors and genital warts in men and women....

  17. Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Schmitz-Winnenthal, Friedrich H; Hohmann, Nicolas; Niethammer, Andreas G; Friedrich, Tobias; Lubenau, Heinz; Springer, Marco; Breiner, Klaus M; Mikus, Gerd; Weitz, Jürgen; Ulrich, Alexis; Buechler, Markus W; Pianka, Frank; Klaiber, Ulla; Diener, Markus; Leowardi, Christine; Schimmack, Simon; Sisic, Leila; Keller, Anne-Valerie; Koc, Ruhan; Springfeld, Christoph; Knebel, Philipp; Schmidt, Thomas; Ge, Yingzi; Bucur, Mariana; Stamova, Slava; Podola, Lilli; Haefeli, Walter E; Grenacher, Lars; Beckhove, Philipp

    2015-04-01

    VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

  18. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients

    Science.gov (United States)

    Mittendorf, E. A.; Clifton, G. T.; Holmes, J. P.; Schneble, E.; van Echo, D.; Ponniah, S.; Peoples, G. E.

    2014-01-01

    Background E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and granulocyte–macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses. Patients and methods The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1–3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan–Meier curves; groups were compared using log-rank tests. Results Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%). Conclusion The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated. Clinical Trials NCT00841399, NCT00584789. PMID:24907636

  19. Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (Ii)

    Science.gov (United States)

    2007-05-01

    uveal melanoma cells. Cancer Res. 67: 4499-4506, 2007. 30. Chamuleau ME, Souwer Y, Van Ham SM, Zevenbergen A, Westers TM, Berkhof J, Meijer CJ, van...MHC class I, class II, CD80, CD4, CD8, and immunoglobulin) or fixed and stained for Ii as described (20). Western blots . Ii Western blots were done...as described (20). Blots for MHC II were done as for Ii with the following modifications: cell lysates were loaded onto SDS-PAGE gels using nonreducing

  20. HPV Vaccine Awareness, Barriers, Intentions, and Uptake in Latina Women.

    Science.gov (United States)

    Lechuga, Julia; Vera-Cala, Lina; Martinez-Donate, Ana

    2016-02-01

    Latina women are at heightened risk of cervical cancer incidence and mortality. The human papillomavirus (HPV) is the principal cause of the majority of cervical cancer cases. A vaccine that protects against HPV was licensed in 2006. Eight years post-licensure, mixed research findings exist regarding the factors that predict vaccine uptake in Latinas. We conducted a population-based phone survey with a random sample of 296 Latinas living in a Midwestern U.S. City. Intention to vaccinate was significantly associated with health care provider recommendations, worry about side effects, knowing other parents have vaccinated, perceived severity of HPV, and worry that daughter may become sexually active following vaccination. Worry that daughter may become sexually active was the only factor related to vaccine uptake. Findings suggest that training providers to discuss the low risk of severe side effects, consequences of persistent HPV, and sexuality related concerns with Latino women may encourage vaccination.

  1. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  2. Vaxvec: The first web-based recombinant vaccine vector database and its data analysis.

    Science.gov (United States)

    Deng, Shunzhou; Martin, Carly; Patil, Rasika; Zhu, Felix; Zhao, Bin; Xiang, Zuoshuang; He, Yongqun

    2015-11-27

    A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development.

  3. Advances in human papilloma virus vaccines: a review

    Directory of Open Access Journals (Sweden)

    Akhilesh Tomar

    2014-02-01

    Full Text Available Cervical cancer is the second most common cancer among women and third leading cause of cancer death. Approximately 500,000 women worldwide develop new cases of cervical cancer annually, with 80% of these new cases occurring in developing countries. Human papilloma virus (HPV infection is the main factor associated with the development of cervical cancer. The currently available HPV vaccines, gardasil and cervarix, can prevent infection by certain HPV types, but not all. At present, research efforts are being devoted to developing broader spectrum preventative vaccines, as well as therapeutic vaccines. To confer additional therapeutic activities, chimeric vaccines have been developed. Multivalent vaccine technologies employ strategies for addressing a broader spectrum of HPV types or for combining HPV with other pathogens. Edible vaccines are also disclosed. For needleless immunization, jet gun, gene gun and microneedles have been developed. Biodegradable and mucoadhesive polymer-based vaccine formulations have been developed to deliver vaccines through the mucosa and enhance immunogenicity. Various viral vectors of recombinant HPV DNA vaccine are disclosed. [Int J Basic Clin Pharmacol 2014; 3(1.000: 37-43

  4. Cellular Immune Response to an Engineered Cell-Based Tumor Vaccine at the Vaccination Site

    OpenAIRE

    Zhou,Qiang; Johnson, Bryon D.; Rimas J Orentas

    2007-01-01

    The engineered expression of the immune co-stimulatory molecules CD80 and CD137L on the surface of a neuroblastoma cell line converts this tumor into a cell-based cancer vaccine. The mechanism by which this vaccine activates the immune system was investigated by capturing and analyzing immune cells responding to the vaccine cell line embedded in a collagen matrix and injected subcutaneously. The vaccine induced a significant increase in the number of activated CD62L− CCR7− CD49b+ CD8 effector...

  5. Therapeutic Vaccine Strategies against Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Hadeel Khallouf

    2014-06-01

    Full Text Available High-risk types of human papillomavirus (HPV cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables, and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches.

  6. Vaccination priorities.

    Science.gov (United States)

    Steffen, Robert; Baños, Ana; deBernardis, Chiara

    2003-02-01

    Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the

  7. Optimization of Ammonium Sulfate Concentration for Purification of Colorectal Cancer Vaccine Candidate Recombinant Protein GA733-FcK Isolated from Plants.

    Science.gov (United States)

    Park, Se-Ra; Lim, Chae-Yeon; Kim, Deuk-Su; Ko, Kisung

    2015-01-01

    A protein purification procedure is required to obtain high-value recombinant injectable vaccine proteins produced in plants as a bioreactor. However, existing purification procedures for plant-derived recombinant proteins are often not optimized and are inefficient, with low recovery rates. In our previous study, we used 25-30% ammonium sulfate to precipitate total soluble proteins (TSPs) in purification process for recombinant proteins from plant leaf biomass which has not been optimized. Thus, the objective in this study is to optimize the conditions for plant-derived protein purification procedures. Various ammonium sulfate concentrations (15-80%) were compared to determine their effects on TSPs yield. With 50% ammonium sulfate, the yield of precipitated TSP was the highest, and that of the plant-derived colorectal cancer-specific surface glycoprotein GA733 fused to the Fc fragment of human IgG tagged with endoplasmic reticulum retention signal KDEL (GA733(P)-FcK) protein significantly increased 1.8-fold. SDS-PAGE analysis showed that the purity of GA733(P)-FcK protein band appeared to be similar to that of an equal dose of mammalian-derived GA733-Fc (GA733(M)-Fc). The binding activity of purified GA733(P)-FcK to anti-GA733 mAb was as efficient as the native GA733(M)-Fc. Thus, the purification process was effectively optimized for obtaining a high yield of plant-derived antigenic protein with good quality. In conclusion, the purification recovery rate of large quantities of recombinant protein from plant expression systems can be enhanced via optimization of ammonium sulfate concentration during downstream processes, thereby offering a promising solution for production of recombinant GA733-Fc protein in plants.

  8. Immune modulations during chemoimmunotherapy & novel vaccine strategies - In metastatic melanoma and non small-cell lung cancer

    DEFF Research Database (Denmark)

    Iversen, Trine Zeeberg

    2013-01-01

    cell responses against well-known MM tumour specific antigens. Overall, we have verified that TMZ in addition to being an alkylating and cytotoxic chemotherapy, also posess immune modulatory effect in MM patients treated with standard dosage of TMZ. In the second part of the thesis we examined how......This thesis describes the treatment of metastatic melanoma (MM) and non small-cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the first part of the thesis was to assess how treatment with Temozolomide (TMZ) chemotherapy affects the immune system in patients...... cells increased. In particular, we demonstrated that mature CD8+ T cells increased during treatment. Analyses of peripheral blood before and after treatment showed that T cell responses against common viral epitopes were conserved despite chemotherapy. Surprisingly, we found a significant increase in T...

  9. Molecular design of allergy vaccines.

    Science.gov (United States)

    Linhart, Birgit; Valenta, Rudolf

    2005-12-01

    Recombinant-allergen-based diagnostic tests enable the dissection and monitoring of the molecular reactivity profiles of allergic patients, resulting in more specific diagnosis, disease monitoring, prevention and therapy. In vitro experiments, animal studies and clinical trials in patients demonstrate that allergenic molecules can be engineered to induce different immune responses ranging from tolerance to vigorous immunity. The available data thus suggest that molecular engineering of the disease-related antigens is a technology that may be applicable not only for the design of allergy vaccines but also for the design of vaccines against infectious diseases, autoimmunity and cancer.

  10. Increasing HPV vaccination through policy for public health benefit.

    Science.gov (United States)

    Brandt, Heather M; Pierce, Jennifer Young; Crary, Ashley

    2016-06-02

    Vaccines against specific types of human papillomavirus (HPV) linked to cancer and other diseases have been met with mixed acceptance globally and in the United States. Policy-level interventions have been shown to be effective in increasing public health benefit. Government policies and mandates may result in improved HPV vaccination coverage and reduced disease burden, and alternative policies that improve unhindered access to HPV vaccination may allow success as well. The purpose of this commentary is to summarize policy efforts to maximize the public health benefit of HPV vaccination. We examine selected examples of HPV vaccination policy in global contexts and in the United States.

  11. Rotavirus Vaccine

    Science.gov (United States)

    ... including a severe allergy to latex. Babies with "severe combined immunodeficiency" (SCID) should not get rotavirus vaccine. Babies who have had a type of bowel blockage called "intussusception" should not get ... with moderate or severe diarrhea or vomiting. Check with your doctor if ...

  12. Polio Vaccine

    Science.gov (United States)

    ... Health Resources Share Polio Vaccine What is polio?Poliomyelitis (polio, for short) is a serious illness that can cause paralysis (when you can't move your arms and legs) or even death. Polio is caused by a virus. The virus can be spread by drinking water ...

  13. Cost-effectiveness of human papillomavirus vaccine in reducing the risk of cervical cancer in Ireland due to HPV types 16 and 18 using a transmission dynamic model

    DEFF Research Database (Denmark)

    Usher, C.; Tilson, L.; Olsen, J.

    2008-01-01

    cost effectiveness of vaccination strategies for 12-year-old females (base-case) and 12-26-year-old catch-up vaccination strategies were examined. The base-case incremental cost-effectiveness ratio was (sic)17,383/LYG. Using a probabilistic sensitivity analysis about the base-case, the 95% CI for cost...... per LYG was ((sic)3400 to E38,400). This suggests that vaccination against HPV types 16 and 18 would be cost-effective from the perspective of the Irish healthcare payer. (C) 2008 Elsevier Ltd. All rights reserved...

  14. Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154

    Directory of Open Access Journals (Sweden)

    Supriya Perambakam

    2010-01-01

    Full Text Available Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P=.02. Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide.

  15. HPV vaccine (Human Papillomavirus) Cervarix® - what you need to know

    Science.gov (United States)

    ... symptoms, and go away on their own. But HPV can cause cervical cancer in women. Cervical cancer is the second leading ... vaccine you are getting is one of two HPV vaccines that can be given to prevent cervical cancer. It is given to females only. The other ...

  16. Varicella (Chickenpox) Vaccine

    Science.gov (United States)

    ProQuad® (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine, Varicella Vaccine) ... up to about 1 person in 5) and measles-like rash (about 1 person in 20) than MMR and varicella vaccines given separately. Moderate Problems:Seizure (jerking or staring) ...

  17. 肿瘤相关抗原在乳腺癌治疗性疫苗中的应用%Application of tumor-associated antigens in breast cancer therapeutic vaccines

    Institute of Scientific and Technical Information of China (English)

    赵洁; 王水

    2013-01-01

    近年来,多种乳腺癌治疗性疫苗进入临床试验阶段,为乳腺癌治疗带来了新的希望.乳腺癌治疗性疫苗的研究,展现了肿瘤相关抗原的优点及其应用特点,同时也提出有待解决的问题.%In recent years,many breast cancer therapeutic vaccines have been entered several clinical trials,which bring a new promising treatment for breast cancer.These trials reveal the advantages and characteristics of tumor-associated antigens,and put forward the questions waiting to be solved.

  18. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines ... or her parents, and the doctor. Why the Vaccines Are Recommended Meningococcal disease is caused by a ...

  19. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines Print ... of Shots? Meningitis How Do I Know Which Vaccines My Kids Need? How Can I Comfort My Baby During ...

  20. Your Baby's First Vaccines

    Science.gov (United States)

    ... of Page Some children should not get certain vaccines Most children can safely get all of these vaccines. But ... has ever had a severe reaction after any vaccination. A child who has a severe (life-threatening) allergy to ...

  1. Vaccines.gov

    Science.gov (United States)

    ... supported by science, on vaccine safety. Are your child’s vaccines up to date? Getting all recommended vaccines on time can protect your child from serious diseases. Protect your community! Did you ...

  2. Vaccines Stop Illness

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  3. Vaccines and Thimerosal

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Thimerosal in Vaccines Recommend on Facebook Tweet Share Compartir Thimerosal is ... harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of vaccine that ...

  4. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....

  5. Social media microblogs as an HPV vaccination forum.

    Science.gov (United States)

    Zhang, Chupei; Gotsis, Marientina; Jordan-Marsh, Maryalice

    2013-11-01

    The 2006 US FDA approval of the human papillomavirus (HPV) vaccine brought new hope for cancer prevention. Gardasil and Cervarix are widely available vaccines that can deter HPV infection, which causes 70% of cervical cancer. Acceptance of vaccination varies due to a lack of HPV awareness and HPV vaccine knowledge. Recent observations of the Chinese microblog "SinaWeibo" suggest a new approach to engage health professionals and consumer website bloggers. Websites that present the latest fashion, fitness or beauty news and ways to obtain "deals" have created informative blogs or online communities that appeal to female users. Some users raise health questions of their peers. Health professionals, as website bloggers, can introduce vaccine news or respond to conversations between bloggers and their followers. By transforming medical vocabulary into ordinary chat, microblogs may promote efficiency in vaccine education and communication. A web-based, interactive social media-microblog could offer an ideal platform to speed up information dissemination and increase targeted communication.

  6. Vaccine-Preventable Disease Photos

    Science.gov (United States)

    Home | About | A-Z | Contact | Follow Vaccine Information You Need VACCINE BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs ...

  7. Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study.

    Science.gov (United States)

    Herweijer, Eva; Sundström, Karin; Ploner, Alexander; Uhnoo, Ingrid; Sparén, Pär; Arnheim-Dahlström, Lisen

    2016-06-15

    Human papillomavirus (HPV) types 16/18, included in HPV vaccines, contribute to the majority of cervical cancer, and a substantial proportion of cervical intraepithelial neoplasia (CIN) grades 2/3 or worse (CIN2+/CIN3+) including adenocarcinoma in situ or worse. The aim of this study was to quantify the effect of quadrivalent HPV (qHPV) vaccination on incidence of CIN2+ and CIN3+. A nationwide cohort of girls and young women resident in Sweden 2006-2013 and aged 13-29 (n = 1,333,691) was followed for vaccination and histologically confirmed high-grade cervical lesions. Data were collected using the Swedish nationwide healthcare registers. Poisson regression was used to calculate incidence rate ratios (IRRs) and vaccine effectiveness [(1-IRR)x100%] comparing fully vaccinated with unvaccinated individuals. IRRs were adjusted for attained age and parental education, and stratified on vaccination initiation age. Effectiveness against CIN2+ was 75% (IRR = 0.25, 95%CI = 0.18-0.35) for those initiating vaccination before age 17, and 46% (IRR = 0.54, 95%CI = 0.46-0.64) and 22% (IRR = 0.78, 95%CI = 0.65-0.93) for those initiating vaccination at ages 17-19, and at ages 20-29, respectively. Vaccine effectiveness against CIN3+ was similar to vaccine effectiveness against CIN2+. Results were robust for both women participating to the organized screening program and for women at prescreening ages. We show high effectiveness of qHPV vaccination on CIN2+ and CIN3+ lesions, with greater effectiveness observed in girls younger at vaccination initiation. Continued monitoring of impact of HPV vaccination in the population is needed in order to evaluate both long-term vaccine effectiveness and to evaluate whether the vaccination program achieves anticipated effects in prevention of invasive cervical cancer.

  8. [Vaccination against mouse pox].

    Science.gov (United States)

    Mahnel, H

    1985-01-01

    Attenuated MVA-strain of vaccinia virus has been efficient in the control of enzootic mousepox and in prophylactic vaccination. The virus has been used as a live vaccine for prophylactic and emergency vaccinations as well as for sanitation of populations. More than 100 000 vaccinations were carried out safely. Even after suspension of the obligatory vaccination of humans against smallpox the MVA-vaccine can be employed without risk and danger.

  9. HPV vaccination to prevent oropharyngeal carcinoma : What can be learned from anogenital vaccination programs?

    NARCIS (Netherlands)

    Takes, Robert P.; Wierzbicka, Malgorzata; D'Souza, Gypsyamber; Jackowska, Joanna; Silver, Carl E.; Rodrigo, Juan P.; Dikkers, Frederik G.; Olsen, Kerry D.; Rinaldo, Alessandra; Brakenhoff, Ruud H.; Ferlito, Alfio

    2015-01-01

    Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was

  10. The HPV Vaccine: Framing the Arguments "for" and "against" Mandatory Vaccination of All Middle School Girls

    Science.gov (United States)

    Vamos, Cheryl A.; McDermott, Robert J.; Daley, Ellen M.

    2008-01-01

    Background: Human papillomavirus (HPV), the virus responsible for cervical cancer, is the most common viral sexually transmitted infection in the United States. A vaccine was approved in 2006 that is effective in preventing the types of HPV responsible for 70% of cervical cancers and 90% of genital warts. Proposals for routine and mandatory HPV…

  11. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  12. Human papillomavirus vaccination in the prevention of cervical neoplasia.

    LENUS (Irish Health Repository)

    Astbury, Katharine

    2012-02-01

    Cervical cancer remains a major cause of morbidity and mortality for women worldwide. Although the introduction of comprehensive screening programs has reduced the disease incidence in developed countries, it remains a major problem in the developing world. The recent licensing of 2 vaccines against human papillomavirus (HPV) type 16 and HPV-18, the viruses responsible for 70% of cervical cancer cases, offers the hope of disease prevention. In this article, we review the role of HPV in the etiology of cervical cancer and the evidence to support the introduction of vaccination programs in young women and discuss the potential obstacles to widespread vaccination. In addition, we discuss the issues that remain to be elucidated, including the potential need for booster doses of the vaccine and the role of concomitant vaccination in men.

  13. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants.

    OpenAIRE

    Marie-Ève Lebel; Karine Chartrand; Denis Leclerc; Alain Lamarre

    2016-01-01

    International audience; Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the develop...

  14. Possible side effects from HPV vaccination in Denmark

    DEFF Research Database (Denmark)

    Hammer, Anne; Petersen, Lone Kjeld; Rolving, Nanna;

    2016-01-01

    HPV vaccination offers protection against ~70% of cervical cancers, however, serious concerns have been raised about the possible side effects from HPV vaccination. Studies have found no increased risk of neurologic disease, autoimmune disorder, thromboembolic disease, postural orthostatic...... tachycardia syndrome, or complex regional pain syndrome in HPV-vaccinated persons compared to unvaccinated persons. Affected individuals should undergo a proper clinical examination to ensure a correct diagnosis and treatment, because symptoms might arise due to a somatic, psychiatric or functional disorder....

  15. Bivirkninger som formodes at skyldes HPV vaccination i Danmark

    DEFF Research Database (Denmark)

    Hammer, Anne; Petersen, Lone Kjeld; Rolving, Nanna;

    2016-01-01

    HPV vaccination offers protection against ~70% of cervical cancers, however, serious concerns have been raised about the possible side effects from HPV vaccination. Studies have found no increased risk of neurologic disease, autoimmune disorder, thromboembolic disease, postural orthostatic...... tachycardia syndrome, or complex regional pain syndrome in HPV-vaccinated persons compared to unvaccinated persons. Affected individuals should undergo a proper clinical examination to ensure a correct diagnosis and treatment, because symptoms might arise due to a somatic, psychiatric or functional disorder....

  16. Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

    Science.gov (United States)

    Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

    2016-09-07

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.