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Sample records for antibodies promising experimental

  1. Single domain antibodies: promising experimental and therapeutic tools in infection and immunity

    OpenAIRE

    Wesolowski, Janusz; Alzogaray, Vanina; Reyelt, Jan; Unger, Mandy; Juarez, Karla; Urrutia, Mariela; Cauerhff, Ana; Danquah, Welbeck; Rissiek, Björn; Scheuplein, Felix; Schwarz, Nicole; ADRIOUCH, Sahil; Boyer, Olivier; Seman, Michel; Licea, Alexei

    2009-01-01

    Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in cam...

  2. Single domain antibodies: promising experimental and therapeutic tools in infection and immunity.

    Science.gov (United States)

    Wesolowski, Janusz; Alzogaray, Vanina; Reyelt, Jan; Unger, Mandy; Juarez, Karla; Urrutia, Mariela; Cauerhff, Ana; Danquah, Welbeck; Rissiek, Björn; Scheuplein, Felix; Schwarz, Nicole; Adriouch, Sahil; Boyer, Olivier; Seman, Michel; Licea, Alexei; Serreze, David V; Goldbaum, Fernando A; Haag, Friedrich; Koch-Nolte, Friedrich

    2009-08-01

    Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in camelid hcAbs and VNAR in shark hcAbs. VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies. The CDR3 region of these sdAbs possesses the extraordinary capacity to form long fingerlike extensions that can extend into cavities on antigens, e.g., the active site crevice of enzymes. Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo. Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes. PMID:19529959

  3. Experimental Drug for Rheumatoid Arthritis Shows Promise

    Science.gov (United States)

    ... medlineplus/news/fullstory_158076.html Experimental Drug for Rheumatoid Arthritis Shows Promise Baricitinib helped patients who failed other ... 2016 (HealthDay News) -- An experimental drug to treat rheumatoid arthritis showed promise in a new six-month trial. ...

  4. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Science.gov (United States)

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  5. Monoclonal Antibody Shows Promise as Potential Therapeutic for MERS | Poster

    Science.gov (United States)

    A monoclonal antibody has proven effective in preventing Middle Eastern Respiratory Syndrome (MERS) in lab animals, suggesting further development as a potential intervention for the deadly disease in humans, according to new research. MERS is a newly emerged coronavirus first detected in humans in 2012. Most cases have occurred in the Middle East, but the disease has appeared elsewhere. In all, MERS has infected more than 1,700 individuals and killed more than 600, according to the World Health Organization. No vaccines or antiviral therapies currently exist. Several candidate vaccines are being developed, and some have been tested in animal models, a prerequisite to human clinical trials.

  6. Monomeric CH3: A Small, Stable Antibody Domain with Therapeutic Promise | Poster

    Science.gov (United States)

    By Ashley DeVine, Staff Writer Antibody domains are emerging as promising biopharmaceuticals because of their relatively small size compared to full-sized antibodies, which are too large to effectively penetrate tumors and bind to sterically restricted therapeutic targets. In an article published in The Journal of Biological Chemistry, Tianlei Ying, Ph.D., Dimiter Dimitrov, Ph.D., and their colleagues in the Protein Interactions Group, Cancer and Inflammation Program, Center for Cancer Research, reported their design of a novel antibody domain, monomeric CH3 (mCH3).

  7. Antibody-Based Biologics and Their Promise to Combat Staphylococcus aureus Infections.

    Science.gov (United States)

    Sause, William E; Buckley, Peter T; Strohl, William R; Lynch, A Simon; Torres, Victor J

    2016-03-01

    The growing incidence of serious infections mediated by methicillin-resistant Staphylococcus aureus (MRSA) strains poses a significant risk to public health. This risk is exacerbated by a prolonged void in the discovery and development of truly novel antibiotics and the absence of a vaccine. These gaps have created renewed interest in the use of biologics in the prevention and treatment of serious staphylococcal infections. In this review, we focus on efforts towards the discovery and development of antibody-based biologic agents and their potential as clinical agents in the management of serious S. aureus infections. Recent promising data for monoclonal antibodies (mAbs) targeting anthrax and Ebola highlight the potential of antibody-based biologics as therapeutic agents for serious infections. PMID:26719219

  8. Promises

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    AT dusk, I switched on my radio. What I heard was a special call-in program entitled "New Air of the City," on a local music channel; the two silver-tongued hosts were discussing the topic of promises. A young woman with a soft voice managed to get through first. She said that she had been in love for many years. She and her fiance often went to the banks of the Yangtze River in their spare time, lifting stones to look for small crabs, as tiny as fingernails. They liked to raise the crabs in a glass bowl. But one day, there were few stones by the river; they searched for a long time, but found nothing. An old man who was catching fish told them that it was difficult to find those crabs on the bank. Then he took several crabs out of his

  9. Experimental Therapy Shows Promise for Type 1 Diabetes

    Science.gov (United States)

    ... Promise for Type 1 Diabetes Complementary Approaches for Depression Featured Website: Prescription Drug Abuse Past Issues Most Viewed June 2016 Print RSS Find us on Facebook External link, please review our exit disclaimer . Subscribe ...

  10. [Early Diagnosis of Osteoarthritis: Clinical Reality and Promising Experimental Techniques].

    Science.gov (United States)

    Arnscheidt, C; Meder, A; Rolauffs, B

    2016-06-01

    It is considered that the structural damage in early osteoarthritis (OA) is potentially reversible. It is therefore particularly important for orthopaedic and trauma surgery to develop strategies and technologies for diagnosing early OA processes. This review presents 3 case reports to illustrate the current clinical diagnostic procedure for OA. Experimental techniques with translational character are discussed in the context of the detection of early degenerative processes relevant to OA. Non-invasive imaging methods such as quantitative MRI, ultrasound, optical coherence tomography (OCT), scintigraphy and diffraction-enhanced synchrotron imaging (DEI), as well as biochemical methods and proteomics, are considered. Early detection of OA is reviewed with minimally invasive techniques, such as arthroscopy, as well as the combination of arthroscopic techniques with indentation, spectrometry, and multiphoton microscopy. In addition, a brief summary of macroscopic and histologic scores is presented. Finally, the spatial organisation of joint surface chondrocytes as an image-based biomarker is used to illustrate an early OA detection strategy that focusses on early changes in tissue architecture potentially prior to damage. In summary, multiple translational techniques are able to detect early OA processes but we do not know whether they truly represent the initial events. Moreover, at this point it is difficult to judge the future clinical relevance of these procedures and to compare their efficacy, as there have been comparative studies. However, the expected gain in knowledge will hopefully help us top attain a more comprehensive understanding of early OA and to develop novel methods for its early diagnosis, therapy, and prevention. Overall, the clinical diagnosis of early OA remains one of the greatest challenges of our field. We still face uncharted territory. PMID:26894867

  11. DNA repair and DNA antibodies during experimental mycoplasma arthritis

    International Nuclear Information System (INIS)

    To clarify the pathogenesis of a mycoplasma induced arthritis in rats, investigations were carried out on the influence of mycoplasma infection on DNA repair and the occurrence of DNA antibodies. During acute and subacute stage of the experimentally induced arthritis an inhibition of DNA repair could be observed. Besides the results indicated a correlation between reduced or inhibited DNA repair and the appearance of DNA antibodies could be found. The DNA-repair behaviour after the mycoplasma infection was compared with the influence of γ-irradiation

  12. Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis.

    Science.gov (United States)

    Bishop, S A; Bailey, M; Lucke, V M; Stokes, C R

    1992-07-01

    An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex-mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were "low", "intermediate" or "high" IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an

  13. Experimental investigations with radiolabeled anti-collagen antibody

    International Nuclear Information System (INIS)

    Antibodies to collagen were prepared and labelled with indium 111. Kinetic studies were performed using labelled antibody for up to 48 hours following an injury. These results provide a method to detect injury by radioimmunographic techniques. 5 figs., 3 tabs

  14. Treponema pallidum-immobilizing antibodies in guinea pig experimental syphilis.

    OpenAIRE

    Wicher, K; Miller, J N; Urquhart, A W; Wicher, V

    1989-01-01

    Treponema pallidum-immobilizing (TPI) antibodies were examined in intradermally infected inbred strain 13 and adoptively immune inbred strain 2 guinea pigs. Both strains of animals produced TPI antibodies at or after 90 days of infection. TPI antibodies were not associated with the protective mechanism(s) operative after challenge in adoptively immune animals.

  15. Radioimmunoimaging of experimental gliomas using radiolabelled monoclonal antibodies

    International Nuclear Information System (INIS)

    The biodistribution and tumour uptake of radiolabelled (131 I) glioma-seeking monoclonal antibodies (14 AC1) and their F(ab')2 fragments were investigated in nude mice having received glioma transplants. Radioimmunoimaging by external scintigraphy at 48 and 96 hours pointed to a superior tumour localisation by the fragments that was clearly related to the dose. Wholebody determinations of the biokinetic behaviour led to the following results: Faster clearance anc more ready elimination from the blood pool for the fragments, preferential uptake in the tumour; intact antibodies; binding in the liver, spleen and lungs. The study confirmed the value of fragments of monoclonal antibodies in the diagnosis of tumours and pointed to the possibility of using intact monoclonal antibodies as carriers of radioisotopes and cytotoxic drugs within the scope of therapeutic programmes. (TRV)

  16. Antibody

    Science.gov (United States)

    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  17. The Effect of CD3-Specific Monoclonal Antibody on Treating Experimental Autoimmune Myasthenia Gravis

    Institute of Scientific and Technical Information of China (English)

    Ruonan Xu; Jianan Wang; Guojiang Chen; Gencheng Han; Renxi Wang; Beffen Shen; Yan Li

    2005-01-01

    CD3-specific monoclonal antibody was the first one used for clinical practice in field of transplantation. Recently,renewed interests have elicited in its capacity to prevent autoimmune diabetes by inducing immune tolerance. In this study, we tested whether this antibody can also be used to treat another kind of autoimmune disease myasthenia gravis (MG) and explored the possible mechanisms. MG is caused by an autoimmune damage mediated by antibody- and complement-mediated destruction of AChR at the neuromuscular junction. We found that administration of CD3-specific antibody (Fab)2 to an animal model with experimental autoimmune myasthenia gravis (EAMG) (B6 mice received 3 times of AChR/CFA immunization) could not significantly improve the clinical signs and clinical score. When the possible mechanisms were tested, we found that CD3 antibody treatment slightly down-regulated the T-cell response to AChR, modestly up-regulation the muscle strength. And no significant difference in the titers of IgG2b was found between CD3 antibody treated and control groups. These data indicated that CD3-specific antibody was not suitable for treating MG, an antibody- and complementmediated autoimmune disease, after this disease has been established. The role of CD3-specific antibody in treating this kind of disease remains to be determined.

  18. Experimental Immunization Based on Plasmodium Antigens Isolated by Antibody Affinity

    Science.gov (United States)

    Kamali, Ali N.; Marín-García, Patricia; Azcárate, Isabel G.; Puyet, Antonio; Diez, Amalia; Bautista, José M.

    2015-01-01

    Vaccines blocking malaria parasites in the blood-stage diminish mortality and morbidity caused by the disease. Here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. We used the sera of malaria self-resistant ICR mice to lethal Plasmodium yoelii yoelii 17XL for purification of their IgGs which were subsequently employed to isolate blood-stage parasite antigens that were inoculated to immunize BALB/c mice. The presence of specific antibodies in vaccinated mice serum was studied by immunoblot analysis at different days after vaccination and showed an intensive immune response to a wide range of antigens with molecular weight ranging between 22 and 250 kDa. The humoral response allowed delay of the infection after the inoculation to high lethal doses of P. yoelii yoelii 17XL resulting in a partial protection against malaria disease, although final survival was managed in a low proportion of challenged mice. This approach shows the potential to prevent malaria disease with a set of antigens isolated from blood-stage parasites. PMID:26539558

  19. Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis

    International Nuclear Information System (INIS)

    A sensitive ''Farr'' assay, utilizing 125I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using 14C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the 125I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested

  20. Kinetics of Anti-Phlebotomus perniciosus Saliva Antibodies in Experimentally Bitten Mice and Rabbits.

    Directory of Open Access Journals (Sweden)

    Inés Martín-Martín

    Full Text Available Sand flies are hematophagous arthropods that act as vectors of Leishmania parasites. When hosts are bitten they develop cellular and humoral responses against sand fly saliva. A positive correlation has been observed between the number of bites and antibody levels indicating that anti-saliva antibody response can be used as marker of exposure to sand flies. Little is known about kinetics of antibodies against Phlebotomus perniciosus salivary gland homogenate (SGH or recombinant salivary proteins (rSP. This work focused on the study of anti-P. perniciosus saliva antibodies in sera of mice and rabbits that were experimentally exposed to the bites of uninfected sand flies.Anti-saliva antibodies were evaluated by ELISA and Western blot. In addition, antibody levels against two P. perniciosus rSP, apyrase rSP01B and D7 related protein rSP04 were determined in mice sera. Anti-saliva antibody levels increased along the immunizations and correlated with the number of sand fly bites. Anti-SGH antibody levels were detected in sera of mice five weeks after exposure, and persisted for at least three months. Anti-apyrase rSP01B antibodies followed similar kinetic responses than anti-SGH antibodies while rSP04 showed a delayed response and exhibited a greater variability among sera of immunized mice. In rabbits, anti-saliva antibodies appeared after the second week of exposure and IgG antibodies persisted at high levels, even 7 months post-exposure.Our results contributed to increase the knowledge on the type of immune response P. perniciosus saliva and individual proteins elicited highlighting the use of rSP01B as an epidemiological marker of exposure. Anti-saliva kinetics in sera of experimentally bitten rabbits were studied for the first time. Results with rabbit model provided useful information for a better understanding of the anti-saliva antibody levels found in wild leporids in the human leishmaniasis focus in the Madrid region, Spain.

  1. Investigation of anti-WI-1 adhesin antibody-mediated protection in experimental pulmonary blastomycosis.

    Science.gov (United States)

    Wüthrich, M; Klein, B S

    2000-05-01

    Infection with Blastomyces dermatitidis elicits strong antibody responses to the surface adhesin WI-1. The antibodies are directed chiefly against the adhesive domain, a 25-amino-acid repeat. Tandem-repeat-specific monoclonal antibodies (mAbs) were studied for their opsonic activity in vitro and their capacity to adoptively transfer protection in murine experimental blastomycosis. mAbs to WI-1 enhanced binding and entry of B. dermatitidis yeasts into J774. 16 cells but did not enhance killing or growth inhibition of the yeast. Passive transfer of 8 mAbs to WI-1 into 3 different inbred strains of mice also did not improve the course of experimental infection and sometimes worsened it. mu-deficient mice were more resistant to experimental blastomycosis than were intact littermates, and passive transfer of the mAbs into these mice did not protect them against experimental infection. Thus, antibody to WI-1 does not appear to improve the outcome of murine blastomycosis and may enhance the infection. PMID:10823774

  2. A radioimmunoassay method for the rapid detection of Candida antibodies is experimental systematic candidiasis

    International Nuclear Information System (INIS)

    Rabbits were employed as experimental models to evaluate a solid-phase radioimmunoassay (RIA) method for the diagnosis of systematic candidiasis. Ten rabbits were incubated subcutaneously to mimic superficial candidiasis and were found to produce no antibodies to Candida as determined by both immunodiffusion and RIA procedures. However, 94 per cent of 18 rabbits systematically infected by intravenous injection of Candida cells were observed to produce antibody as assessed by the RIA technique. These data encourage further tests with human sera and the continued development of this RIA procedure as a useful tool in the early serodiagnosis of systematic candidiasis. (Auth.)

  3. Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Gust, I.D.; Feinstone, S.M.; Purcell, R.H.; Alter, H.J.

    1980-01-01

    A sensitive ''Farr'' assay, utilizing /sup 125/I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using /sup 14/C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the /sup 125/I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.

  4. Experimental studies of low salinity water flooding in carbonate reservoirs: A new promising approach

    DEFF Research Database (Denmark)

    Zahid, Adeel; Shapiro, Alexander; Skauge, Arne

    2012-01-01

    Low salinity water flooding is well studied for sandstone reservoirs, both laboratory and field tests have showed improvement in the oil recovery in many cases. Up to very recently, the low salinity effect has been indeterminated for carbonates. Most recently, Saudi Aramco reported that substanti...... light of experimental results, discussions are made about possible mechanisms for improving oil recovery in carbonate reservoir as a function of change in brine salinity. Copyright 2012, Society of Petroleum Engineers....

  5. Monoclonal antibody against Klebsiella capsular polysaccharide reduces severity and hematogenic spread of experimental Klebsiella pneumoniae pneumonia.

    OpenAIRE

    Held, T K; Trautmann, M.; Mielke, M E; Neudeck, H; Cryz, S J; Cross, A S

    1992-01-01

    Klebsiella pneumoniae is an important nosocomial pathogen causing severe pulmonary infections. The majority of clinical Klebsiella isolates produce a high-molecular-weight capsular polysaccharide (CPS) which is one of the dominant virulence factors. In the present study, we examined the potency of a murine immunoglobulin M monoclonal antibody (MAb) with specificity to Klebsiella type 2 CPS to protect rats against experimental Klebsiella pneumonia. The MAb did not prevent the invasion of virul...

  6. Influence of preformed antibody on the pathogenesis of experimental Candida albicans endocarditis.

    OpenAIRE

    Scheld, W M; Calderone, R A; Brodeur, J P; Sande, M A

    1983-01-01

    The influence of preformed antibody on the induction of experimental Candida albicans endocarditis was investigated by both in vitro and in vivo techniques. Preincubation of C. albicans with immune serum (raised in rabbits by intravenous injection of Formalin-killed yeast cells) decreased adhesion to the constituents of nonbacterial thrombotic endocarditis, e.g., fibrin plus platelets, in vitro. Two different methods, with radiolabeled or viable yeast cells, were confirmatory and demonstrated...

  7. Sensory perception in cetaceans: Part II – Promising experimental approaches to study chemoreception in dolphins

    Directory of Open Access Journals (Sweden)

    Dorothee eKremers

    2016-05-01

    Full Text Available Chemosensory perception in cetaceans remains an intriguing issue as morphological, neuroanatomical and genetic studies draw unclear conclusions, while behavioral data suggest that dolphins may use it for food selection or socio-sexual interactions. Experimental approaches have been scarce due to the practical difficulties of testing chemoreception in wild dolphins. Go/no-go tasks are one elegant way to investigate discrimination abilities; however, they require to train the animals, thus preventing spontaneous responses and hence the expression of preferences. Here, we aimed at testing potential spontaneous responses to chemical stimuli and developed novel procedures. First, we conducted a study to test whether captive dolphins respond to a biologically relevant smell. Therefore, we placed dead fish within an opaque barrel at the border of the pool and counted the number of respirations at proximity as an indicator of investigation. The same dead fishes were presented several times during experiments lasting three consecutive days. From the second day on (i.e. when the odor composition changed, dolphins breathed more often close to the fish-smelling barrel than close to the visually identical but empty control barrel. Second, we conducted a study to test whether dolphins are able to discriminate food flavors. Captive dolphins are commonly provided with ice cubes as a source of enrichment. We took this opportunity to provide ice cubes with different flavors and to compare the reaction to these different flavors as a measure of discrimination. Hence, we used the latency of return to the ice cube begging spot as a measure of discrimination from the previous ice cube flavor. Thus, our method used a non-invasive and easily replicable technique based on the spontaneous begging responses of dolphins toward more or less attractive items bearing biological relevance. The procedures used enabled us to show that dolphins may discriminate odors and flavors

  8. Antibody and inflammatory responses in laying hens with experimental primary infections of Ascaridia galli.

    Science.gov (United States)

    Marcos-Atxutegi, C; Gandolfi, B; Arangüena, T; Sepúlveda, R; Arévalo, M; Simón, F

    2009-04-01

    Ascaridia galli, an intestinal nematode that affects hens and other domestic and wild birds, causes economic losses in avian exploitations. The present work shows that A. galli stimulates a strong antibody response as well as an intense inflammatory reaction, in the intestinal mucous of experimentally infected Lohmann Brown laying hens. IgG antibodies against soluble extracts of A. galli embrionated eggs and adult worms, were detected in both blood and yolks eggs from infected hens during a period of 105 days after the infection. This indicates that hens transfer to their offspring a part of the IgG antibodies produced when they become infected. The antigens responsible for the stimulation of specific IgG were molecules of 30-34, 44-54 and 58-90 kDa, while in the yolk eggs of infected hens a reactivity directed against antigens of molecular weight (M(w)) lower than 50 kDa was detected. Histology revealed traumatic lesions with leukocyte infiltration, and inflammation of the intestinal wall of the infected hens after 105 days of initial infection. The possible influence of the immune and inflammatory response on the population dynamics of the parasite is discussed. PMID:19167166

  9. Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Wong, D.W.; Dhawan, V.K.; Tanaka, T.; Mishkin, F.S.; Reese, I.C.; Thadepalli, H.

    1982-03-01

    The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.

  10. Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication

    International Nuclear Information System (INIS)

    The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis

  11. Nerve growth factor antibody exacerbates neuropathological signs of experimental allergic encephalomyelitis in adult lewis rats.

    Science.gov (United States)

    Micera, A; Properzi, F; Triaca, V; Aloe, L

    2000-05-01

    In this study, experimental allergic encephalomyelitis (EAE) rats and rats exhibiting EAE expressing high circulating anti-nerve growth factor antibody were daily monitored for clinical signs and chronic relapses. Eighty-five days after EAE induction, blood, spinal cord and brain stem were used for histological examination, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) evaluation. The results showed that NGF-deprived rats display more severe clinical signs of disease. These effects were associated with a significant reduction of NGF in the brain stem and spinal cord but not of BDNF, which decreased only in spinal cord. These observations provide additional support to the hypothesis of a protective NGF role in rats exhibiting EAE. PMID:10713350

  12. A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia.

    OpenAIRE

    Brown, E J; Hosea, S W; Hammer, C H; Burch, C G; Frank, M M

    1982-01-01

    The mechanism of protection of type-specific antipneumococcal antibody and complement in bacteremia was investigated with purified rabbit antibody and a guinea pig model of pneumococcal bacteremia. IgG and IgM were isolated from the sera of rabbits immunized with type 7 pneumococci (Pn), and their binding to Pn was quantitated. The number of antibody-binding sites on the pnuemococcal capsule was also determined. Pn were incubated with various amounts of the immunoglobulin preparations before ...

  13. Fuzzy promises

    DEFF Research Database (Denmark)

    Anker, Thomas Boysen; Kappel, Klemens; Eadie, Douglas;

    2012-01-01

    This article clarifies the commonplace assumption that brands make promises by developing definitions of brand promise delivery. Distinguishing between clear and fuzzy brand promises, we develop definitions of what it is for a brand to deliver on fuzzy functional, symbolic, and experiential...... promises. We argue (a) that brands deliver fuzzy functional promises through encouraging and facilitating courses of actions that are conducive to the promised functionality; whereas (b) brands deliver fuzzy symbolic promises through encouraging and facilitating ways in which consumers can use brands as...... narrative material to communicate self-identity. Finally, (c) we propose that brands deliver fuzzy experiential promises through effectively motivating consumers to adopt and play a social role implicitly suggested and facilitated by the brand. A promise is an inherently ethical concept and the article...

  14. Local immunotherapy based on agonistic CD40 antibodies effectively inhibits experimental bladder cancer

    OpenAIRE

    Sandin, Linda C; Tötterman, Thomas H; Sara M. Mangsbo

    2014-01-01

    Local immunotherapy resurfaces in the field of cancer as a potential way to cure localized and metastatic disease with limited toxic effects. We have recently demonstrated that local administration of agonistic CD40 antibodies can cure localized as well as disseminated bladder neoplasms. This approach reduces the circulating concentrations of antibodies that would result from systemic delivery, hence resulting in limited toxicity.

  15. Experimental radioimmunotherapy of a xenografted human glioma using 131I-labeled monoclonal antibody to epidermal growth factor receptor

    International Nuclear Information System (INIS)

    131I-labeled F (ab')2 fragments of murine monoclonal antibodies (MAb) 425 specific to the epidermal growth factor receptor expressed on human gliomas were used in experimental human malignant glioma immunotherapy. Two injections of 150 μCi 131I-labeled 425 F(ab')2 achieved growth inhibition of U-87MG human malignant glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')2 was significantly superior to radiolabeled fragments of an anti-hepatitis virus control MAb A5C3 in influencing tumor growth. However, similar treatment of established human malignant glioma xenografts did not inhibit progressive tumor growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425F(ab')2. These studies suggest that 131I-labeled MAbs have a significant antitumor effect where unmodified antibody is ineffective. Multiple doses of antibody may achieve an increase in labeled MAb concentration in tumors. (author)

  16. Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

    DEFF Research Database (Denmark)

    Uysal, Hüseyin; Bockermann, Robert; Nandakumar, Kutty S;

    2009-01-01

    Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical...... collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII is...

  17. Trypanosoma cruzi infection in the opossum Didelphis marsupialis: absence of neonatal transmission and protection by maternal antibodies in experimental infections

    Directory of Open Access Journals (Sweden)

    Ana M. Jansen

    1994-03-01

    Full Text Available The high rate of natural Trypanosoma cruzi infection found in opossums does not always correlate with appreciable densities of local triatomid populations. One alternative method which might bypass the invertebrate vector is direct transmission from mother to offspring. This possibility was investigated in five T. cruzi infected females and their litters (24 young. The influence of maternal antibodies transferred via lactation, on the course of experimental infection, was also examined. Our results show that neonatal transmission is probably not responsible for the high rate of natural T. cruzi infection among opossums. In addition antibodies of maternal origin confer a partial protection to the young. This was demonstrated by the finding of a double prepatency period and 4,5 fold lower levels of circulating parasites, in experimentally infected pouch young from infected as compared to control uninfected mothes. On the other hand, the duration of patent parasitemia was twice as long as that observed in the control group.

  18. An experimental design approach to optimize an amperometric immunoassay on a screen printed electrode for Clostridium tetani antibody determination.

    Science.gov (United States)

    Patris, Stéphanie; Vandeput, Marie; Kenfack, Gersonie Momo; Mertens, Dominique; Dejaegher, Bieke; Kauffmann, Jean-Michel

    2016-03-15

    An immunoassay for the determination of anti-tetani antibodies has been developed using a screen printed electrode (SPE) as solid support for toxoid (antigen) immobilization. The assay was performed in guinea pig serum. The immunoreaction and the subsequent amperometric detection occurred directly onto the SPE surface. The assay consisted of spiking the anti-tetani sample directly onto the toxoid modified SPE, and then a second antibody, i.e. a HRP-labeled anti-immunoglobulin G, was deposited onto the biosensor. Subsequent amperometric detection was realized by spiking 10 µL of a hydroquinone (HQ) solution into 40 µL of buffer solution containing hydrogen peroxide. An experimental design approach was implemented for the optimization of the immunoassay. The variables of interest, such as bovine serum albumin (BSA) concentration, incubation times and labeled antibody dilution, were optimized with the aid of the response surface methodology using a circumscribed central composite design (CCCD). It was observed that two factors exhibited the greatest impact on the response, i.e. the anti-tetani incubation time and the dilution factor of the labeled antibody. It was discovered that in order to maximize the response, the dilution factor should be small, while the anti-tetani antibody incubation time should be long. The BSA concentration and the HRP-anti-IgG incubation had very limited influence. Under the optimized conditions, the immunoassay had a limit of detection of 0.011 IU/mL and a limit of quantification of 0.012 IU/mL. These values were below the protective human antibody limit of 0.06 IU/mL. PMID:26454827

  19. Experimental results of antigliadin antibodies detection using long period fiber grating

    Science.gov (United States)

    Corres, J. M.; Matias, I. R.; Goicoechea, J.; Arregui, F. J.; Viegas, D.; Araújo, F. M.; Santos, J. L.

    2008-04-01

    In this work a new nano-biofilm is proposed for the detection of celiac disease (CD). A long-period fiber grating (LPFG) is used as a transducer and the surface of the fiber is coated with a precursor layer of SiO2-nanospheres using the electrostatic self-assembly technique (ESA). This layer has been designed in order to create a substrate of high porosity where the gliadins could be deposited. Under the presence of specific antibodies antigliadin antibodies (AGA) the refractive index of the overlay changes giving a detectable shift in the resonance wavelength of the LPFG. Concentrations as low as 5 ppm were detected.

  20. An Experimental Study on Production of Egg Yolk Antibody(IgY) against Bee Venom

    OpenAIRE

    Hwang, Tae-Jun; Lee, Seung-bae; Gwon, Gi-Rok

    2001-01-01

    This study was carried out for production of neutral antibody to bee venom(anti-phospholipase A2 IgY). Hen layings were injected repeatedly with bee venom and phospholipase A2 with Freund's adjuvant. Specific antibody in egg yolk from immunized hen laying was separated, and purified, also immunological characteristics of anti-phospholipase A2 IgY was invested. The results were summarized as follows : 1. Phospholipase A2 was showed single band at molecular weight 17,000 in SDS-PAGE and b...

  1. Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.

    Science.gov (United States)

    Walker, Karen M; Okitsu, Shinji; Porter, David W; Duncan, Christopher; Amacker, Mario; Pluschke, Gerd; Cavanagh, David R; Hill, Adrian V S; Todryk, Stephen M

    2015-05-01

    This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related. PMID:25471322

  2. Experimental comparison of three background subtraction agents for monoclonal antibody imaging of ovarian carcinoma xenografts

    International Nuclear Information System (INIS)

    Dual-isotope background subtraction imaging can be used to enhance lesion detection in imaging studies using monoclonal antibodies. The best agent for background subtraction has not been determined, however. The author compared Tc-99m human serum albumin, Tc-99m red blood cells, and I-123-labeled nonspecific murine myeloma immunoglobulin (UPC-10) for their ability to enhance imaging of ovarian carcinoma xenografts in groups of nude mice 24 hours after they were injected with I-131 5G6.4 tumor-specific intact immunoglobulin. Using dual-isotope dynamic background subtraction, tumor imaging was most clear with Tc-99m red blood cells, second best with Tc-99m human serum algumin, and least clear with I-123 UPC-10. while verification in humans will be essential, these animal findings suggest that dual-isotope monoclonal antibody imaging of tumors is enhanced most with Tc-99m red blood cells and least with an isotype-matched monoclonal antibody

  3. Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response.

    Science.gov (United States)

    Zhuang, Xiaohui; Shen, Jiaqing; Jia, Zhengyu; Wu, Airong; Xu, Ting; Shi, Yuqi; Xu, Chunfang

    2016-06-01

    B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway, and ameliorated the pancreas disruption in l-arginine-induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l-arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response. PMID:27003113

  4. Effects of experimental immunosuppression in cattle with persistently high antibody levels to Salmonella Dublin lipopolysaccharide O-antigens

    Directory of Open Access Journals (Sweden)

    Nielsen Liza R

    2007-08-01

    Full Text Available Abstract Background Salmonella Dublin (S. Dublin is a zoonotic bacterium which is host adapted to cattle. The bacterium can cause subclinical persistent infection in cattle (carriers, which may be reactivated. During reactivation, animals may shed bacteria, thus constituting a source of infection for other animals. Identification of such carriers is assumed to be critical in attempts to control and eradicate the infection. Some authors suggest that persistently high antibody levels in serum or milk is indicative of a carrier state in cattle. However, this has been questioned by other studies in which S. Dublin were not found in all animals suspected of being carriers based on antibody measurements when such animals were examined at slaughter. Some hypothesize that the lack of isolated bacteria from long-term high antibody level cattle is due to a latent infection stage that can later be reactivated, for instance during stress around calving or due to transportation. This study examined nine adult cattle with persistently high antibody responses to S. Dublin O-antigen based lipopolysaccharide for cultivable bacteria in faeces, milk and internal organs before and after transportation, isolation and experimental immunosuppression with dexamethasone sodium phosphate over a period of 7–14 days. Results Clear signs of immunosuppression were seen as expression of leucocytosis and neutrophilia in all animals on day 3–5 after the first injections with dexamethasone sodium phosphate. No clinical signs or necropsy findings indicating salmonellosis were observed in any of the animals. No shedding of S. Dublin was found in faeces (collected four times daily or milk (collected twice daily at any point in time during the 7–14 day period. S. Dublin was recovered by a conventional culture method from tissue samples from mammary lymph nodes, spleen and liver collected from three animals at necropsy. Conclusion In this study, immunosuppression by

  5. MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.

    Science.gov (United States)

    Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yılmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T; Finkelman, Fred D; Kabadayı, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar

    2016-06-15

    Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. PMID:27235354

  6. INHIBITION OF HUMAN EXPERIMENTAL GASTRIC CARCINOMA METASTASIS IN VIVO BY P-SELECTIN MONOCLONAL ANTIBODY

    Institute of Scientific and Technical Information of China (English)

    陈金联; 陈维雄; 朱金水; 陈尼维; 姚明; 周同

    2001-01-01

    Objeetive To study the role of cell adhesion molecule P-selectin monoclonal antibody ( MAb ) in tumor metastasis of an orthotopic metastatic model. Methods SCID mice were implanted orthotopically SGC-7901 human gastric cancer tissue. 3d later, animals received i. v. injections of PBS or P-selectin MAb ( 100μg /injection ) twice weekly for 3 weeks. 42d after operation, all animals were sacrificed. Tissues from all organs were obtained for histopathological evaluation. Results 10 of the animals ( n = 11 ) treated with PBS were found to develop metastatic tumors in the regional lymph nodes, liver, and lung. In contrast, 2 of the animals ( n = 9 ) treated with P-selectin MAb developed metastatic tumors in the organs examined. The expression of P-selectin mRNA in gastric cancer tissue of SCID mice with tumor metastasis was higher than that without such metastasis. Conclusion P-selectin expression is associated with tumor metastasis, and the metastasis may be inhibited by the MAb.

  7. Reporting research antibody use: how to increase experimental reproducibility [v1; ref status: indexed, http://f1000r.es/1fj

    Directory of Open Access Journals (Sweden)

    Matthew A Helsby

    2013-07-01

    Full Text Available Research antibodies are used in a wide range of bioscience disciplines, yet it is common to hear dissatisfaction amongst researchers with respect to their quality. Although blame is often attributed to the manufacturers, scientists are not doing all they can to help themselves. One example of this is in the reporting of research antibody use. Publications routinely lack key details, including the host species, code number and even the company who supplied the antibody. Authors also fail to demonstrate that validation of the antibodies has taken place. These omissions make it harder for reviewers to establish the likely reliability of the results and for researchers to reproduce the experiments. The scale of this problem, combined with high profile concerns about experimental reproducibility, has caused the Nature Publishing Group to include a section on antibody information in their recent Reporting Checklist for Life Science Articles. In this commentary we consider the issue of reporting research antibody use and ask what details authors should be including in their publications to improve experimental reproducibility.

  8. Experimental and in silico modelling analyses of the gene expression pathway for recombinant antibody and by-product production in NS0 cell lines.

    Directory of Open Access Journals (Sweden)

    Emma J Mead

    Full Text Available Monoclonal antibodies are commercially important, high value biotherapeutic drugs used in the treatment of a variety of diseases. These complex molecules consist of two heavy chain and two light chain polypeptides covalently linked by disulphide bonds. They are usually expressed as recombinant proteins from cultured mammalian cells, which are capable of correctly modifying, folding and assembling the polypeptide chains into the native quaternary structure. Such recombinant cell lines often vary in the amounts of product produced and in the heterogeneity of the secreted products. The biological mechanisms of this variation are not fully defined. Here we have utilised experimental and modelling strategies to characterise and define the biology underpinning product heterogeneity in cell lines exhibiting varying antibody expression levels, and then experimentally validated these models. In undertaking these studies we applied and validated biochemical (rate-constant based and engineering (nonlinear models of antibody expression to experimental data from four NS0 cell lines with different IgG4 secretion rates. The models predict that export of the full antibody and its fragments are intrinsically linked, and cannot therefore be manipulated individually at the level of the secretory machinery. Instead, the models highlight strategies for the manipulation at the precursor species level to increase recombinant protein yields in both high and low producing cell lines. The models also highlight cell line specific limitations in the antibody expression pathway.

  9. Experimental and in silico modelling analyses of the gene expression pathway for recombinant antibody and by-product production in NS0 cell lines.

    Science.gov (United States)

    Mead, Emma J; Chiverton, Lesley M; Spurgeon, Sarah K; Martin, Elaine B; Montague, Gary A; Smales, C Mark; von der Haar, Tobias

    2012-01-01

    Monoclonal antibodies are commercially important, high value biotherapeutic drugs used in the treatment of a variety of diseases. These complex molecules consist of two heavy chain and two light chain polypeptides covalently linked by disulphide bonds. They are usually expressed as recombinant proteins from cultured mammalian cells, which are capable of correctly modifying, folding and assembling the polypeptide chains into the native quaternary structure. Such recombinant cell lines often vary in the amounts of product produced and in the heterogeneity of the secreted products. The biological mechanisms of this variation are not fully defined. Here we have utilised experimental and modelling strategies to characterise and define the biology underpinning product heterogeneity in cell lines exhibiting varying antibody expression levels, and then experimentally validated these models. In undertaking these studies we applied and validated biochemical (rate-constant based) and engineering (nonlinear) models of antibody expression to experimental data from four NS0 cell lines with different IgG4 secretion rates. The models predict that export of the full antibody and its fragments are intrinsically linked, and cannot therefore be manipulated individually at the level of the secretory machinery. Instead, the models highlight strategies for the manipulation at the precursor species level to increase recombinant protein yields in both high and low producing cell lines. The models also highlight cell line specific limitations in the antibody expression pathway. PMID:23071804

  10. In vitro experimental {sup 211}At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

    Energy Technology Data Exchange (ETDEWEB)

    Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Meyer, Geerd J.; Knapp, Wolfram H. [Hanover University School of Medicine, Department of Nuclear Medicine, Hanover (Germany); Froemke, Cornelia [Hanover University School of Medicine, Department of Biometry, Hanover (Germany)

    2010-05-15

    Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter {sup 211}At and compared survival of leukaemic HL-60 and K-562 cells treated with the {sup 211}At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free {sup 211}At. The mean labelling ratio of {sup 211}At-labelled antibodies was 1:1,090 {+-} 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of {sup 211}At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. {sup 211}At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after {sup 211}At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that {sup 211}At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase {sup 211}At-anti-CD33 therapeutic effects. (orig.)

  11. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Ma Jun [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Tian Weiming [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Hou Shaoping [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing 100054 (China); Xu Qunyuan [Beijing Institute of Neuroscience, Capital University of Medical Sciences, Beijing 100054 (China); Spector, Myron [Tissue Engineering, VA Boston Healthcare System, Harvard Medical School, Boston, MA (United States); Cui Fuzhai [Biomaterials Laboratory, Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2007-12-15

    The objective of the study was to determine the effects of a hyaluronic-acid-based (HA-based) hydrogel implant, carrying a polyclonal antibody to the Nogo-66 receptor (NgR), on adult rats that underwent middle cerebral artery occlusion (MCAO). Behavioral tests of a forelimb-reaching task suggested that the disabled function of the impaired forelimb in this stroke model was ameliorated by the implant to a certain extent. These behavioral findings were correlated with immunohistochemical results of investigating the distribution of NgR antibody, neurofilaments (NF) and neuron-specific class III {beta}-tubulin (TuJ1) in the brain sections. The porous hydrogel functioned as a scaffold to deliver the NgR antibody, support cell migration and development. In addition, it was found NF-positive and TuJ1-positive expressions were distributed in the implanted hydrogel. Collectively, the results demonstrate the promise of the HA hydrogel as a scaffold material and the delivery vehicle of the NgR antibody for the repair of defects and the support of neural regeneration in the brain.

  12. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model

    International Nuclear Information System (INIS)

    The objective of the study was to determine the effects of a hyaluronic-acid-based (HA-based) hydrogel implant, carrying a polyclonal antibody to the Nogo-66 receptor (NgR), on adult rats that underwent middle cerebral artery occlusion (MCAO). Behavioral tests of a forelimb-reaching task suggested that the disabled function of the impaired forelimb in this stroke model was ameliorated by the implant to a certain extent. These behavioral findings were correlated with immunohistochemical results of investigating the distribution of NgR antibody, neurofilaments (NF) and neuron-specific class III β-tubulin (TuJ1) in the brain sections. The porous hydrogel functioned as a scaffold to deliver the NgR antibody, support cell migration and development. In addition, it was found NF-positive and TuJ1-positive expressions were distributed in the implanted hydrogel. Collectively, the results demonstrate the promise of the HA hydrogel as a scaffold material and the delivery vehicle of the NgR antibody for the repair of defects and the support of neural regeneration in the brain

  13. The time course of the specific antibody response by various ELISAs in pigs experimentally infected with Toxoplasma gondii

    DEFF Research Database (Denmark)

    Lind, Peter; Haugegaard, J.; Wingstrand, Anne;

    1997-01-01

    With the aim of developing routine serological tests for monitoring the Toxoplasma infection status of Danish swine herds, four ELISAs based on tachyzoite antigen were set up: (1) an indirect ELISA for IgG-antibody; (2) a blocking ELISA for antibody to the membrane antigen, P-30; (3) an indirect ...

  14. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    2016-01-01

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology. PMID:27236550

  15. Serological response of cats to experimental Besnoitia darlingi and Besnoitia neotomofelis infections and prevalence of antibodies to these parasites in cats from Virginia and Pennsylvania.

    Science.gov (United States)

    Houk, Alice E; Rosypal, Alexa C; Grant, David C; Dubey, J P; Zajac, Anne M; Yabsley, Michael J; Lindsay, David S

    2011-04-01

    Besnoitia darlingi and Besnoitia neotomofelis are cyst-forming tissue apicomplexan parasites that use domestic cats (Felis domesticus) as definitive hosts and opossums (Didelphis virginiana ) and Southern Plains woodrats (Neotoma micropus) as intermediate hosts, respectively. Nothing is known about the prevalence of B. darlingi or B. neotomofelis in cats from the United States. Besnoitia darlingi infections have been reported in naturally infected opossums from many states in the United States, and B. neotomofelis infections have been reported from Southern Plains woodrats from Texas, but naturally infected cats have not been identified. The present study examined the IgG antibody response of cats to experimental infection (B. darlingi n  =  1 cat; B. neotomofelis n  =  3 cats). Samples from these cats were used to develop an indirect immunofluorescent antibody test (IFAT), which was then used to examine seroprevalence of IgG antibodies to tachyzoites of B. darlingi and B. neotomofelis in a population of domestic cats from Virginia (N  =  232 cats) and Pennsylvania (N  =  209). The serum from cats inoculated with B. darlingi or B. neotomofelis cross-reacted with each other's tachyzoites. The titers to heterologous tachyzoites were 1 to 3 dilutions lower than to homologous tachyzoites. Sera from B. darlingi- or B. neotomofelis-infected cats did not react with tachyzoites of Toxoplasma gondii or Neospora caninum or merozoites of Sarcocystis neurona using the IFAT. Antibodies to B. darlingi were found in 14% and 2% of cats from Virginia and Pennsylvania, respectively. Antibodies to B. neotomofelis were found in 5% and 4% of cats from Virginia and Pennsylvania, respectively. Nine cats from Virginia and 1 cat from Pennsylvania were positive for both. PMID:21506782

  16. Thyroid Antibodies

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  17. [Serological demonstration of experimental round worm infections-Ascaris suum, Toxocara canis--in swine by means of the indirect immunofluorescence antibody test].

    Science.gov (United States)

    Buchwalder, R; Matthes, H F; Hiepe, T

    1981-11-01

    By means of indirect immunofluorescent antibody reaction (IFAR), using serum of experimentally infected pigs, various antigens were studied with regard to their usefulness for serological verification of prepatent Ascaris suum and Toxocara canis infections. Eggs, egg larvae, larvae received from livers, lungs and brains of experimentally infected white mice and sections of adult T. canis as well as eggs, egg larvae, liver larvae and sections of frozen adult A. suum proved to be not suitable for the reliable serum diagnosis of the infections. On the other hand, A. suum larvae, isolated from lungs of white mice or guinea pigs days after experimental infection, represent an antigen applicable to IFAR for the evidence of prepatent A. suum infections in pigs. The antigen, stored at -20 degree C, is durable without substantial impairment of its reactivity at least 7 months. PMID:7039425

  18. Protective role of antimannan and anti-aspartyl proteinase antibodies in an experimental model of Candida albicans vaginitis in rats.

    OpenAIRE

    De Bernardis, F.; Boccanera, M; Adriani, D; Spreghini, E; G. Santoni; Cassone, A.

    1997-01-01

    The role of antibodies (Abs) in the resistance to vaginal infection by Candida albicans was investigated by using a rat vaginitis model. Animals receiving antimannoprotein (anti-MP) and anti-aspartyl proteinase (Sap) Ab-containing vaginal fluids from rats clearing a primary C. albicans infection showed a highly significant level of protection against vaginitis compared to animals given Ab-free vaginal fluid from noninfected rats. Preabsorption of the Ab-containing fluids with either one or bo...

  19. Combinations of nonlabeled, 125I-labeled, and anti-idiotypic antiplacental alkaline phosphatase monoclonal antibodies at experimental radioimmunotargeting

    International Nuclear Information System (INIS)

    Purpose: Placental alkaline phosphatase (PLAP) is a membrane-bound oncofetal antigen that can be used for radioimmunotargeting. Preinjection of nonlabeled monoclonal anti-PLAP antibody (H7) and postinjection of monoclonal anti-idiotypic anti-PLAP antibody (αH7) were used in order to improve the localization efficacy of 125I-labeled H7. Material and Methods: A human cervix adenocarcinoma cell line (HeLa Hep 2) was inoculated subcutaneously in 24 nude mice. Repeated quantitative radioimmunoscintigraphic recordings were performed on 27 occasions in each of the 24 mice during the observation period which lasted for nearly 3 months. The tumor and nontumor doses were calculated according to the Medical International Radiation Dose Committee formula on the basis of the scintigraphic data. Results: All tumors were clearly visualized as early as one day after injection of 125I-labeled H7. The remaining radioactivity was exclusively located in the tumors at days 30-81. As much as 12-16% of the injected dose/g accumulated in the tumors during the first 2 days after injection, and remained stable at this high level for approximately 10 days in all investigated groups. Radioactivity in the whole body was rapidly eliminated during the same time period. The highest tumor/nontumor dose ratio was obtained after a single injection of 125I-labeled H7. Conclusion: Neither a preinjection of nonlabeled H7 nor a postinjection of αH7 nor a combination of both strategies resulted in improved tumor/nontumor dose ratios compared to a single injection of labeled H7. The monoclonal antibody H7 has a rapid and high uptake, combined with a prolonged retention time in the tumors. The kinetic properties of H7 are different form antibodies targeting intracellular tumor antigens. (orig.)

  20. Antibody Responses of Cervids (Cervus elaphus) following Experimental Mycobacterium bovis Infection and the Implications for Immunodiagnosis ▿

    OpenAIRE

    Harrington, Noel P.; Surujballi, Om P.; Prescott, John F.; Duncan, J. Robert; Waters, W. Ray; Lyashchenko, Konstantin; Greenwald, Rena

    2008-01-01

    Captive and free-ranging wildlife animals are implicated in the maintenance and transmission of bovine tuberculosis and therefore pose a significant obstacle to eradication of the disease from domestic livestock. The current antemortem diagnostic method, the intradermal tuberculin skin test, is impractical for routine use with many wild animals. Antibody-based assays are particularly attractive because the animals are handled only once and immediate processing of the sample is not required. T...

  1. Continuing experimental investigations with radiolabeled anti-collagen antibodies and related antibodies: Progress report, May 1, 1987 through November 30, 1987

    International Nuclear Information System (INIS)

    The basic research goal is to develop an in vivo probe with histopathologic correlates that can be used to characterize irradiation lung injury. Irradiation lung injury is a very important problem in patients receiving total body irradiation prior to bone marrow transplantation for diseases such as leukemia. Basic research defining irradiation lung injury will have important clinical significance. We have developed a simple jig to hold the Sprague-Dawley rat during irradiation, and have successfully shielded all but the right lung. Dosimetry studies were performed and we found that we were delivering a dose to the rats mid-lung of 1 Gy/min from the experimental therapy machine. We confirmed the region of pulmonary irradiation not only with radiographic studies of the jig in place, but also with injections of technetium-labeled-MASS in some of our 25-day rats. This showed a profound perfusion deficit compatible with irradiation involving the entire right lung confirming successful placement of the irradiation portal. All of the experiments we describe employed a dose of 25 Gy. 1 fig., 3 tabs

  2. Relative disease susceptibility and clostridial toxin antibody responses in three commercial broiler lines coinfected with Clostridium perfringens and Eimeria maxima using an experimental model of necrotic enteritis.

    Science.gov (United States)

    Jang, Seung I; Lillehoj, Hyun S; Lee, Sung-Hyen; Lee, Kyung Woo; Lillehoj, Erik P; Hong, Yeong Ho; An, Dong-Jun; Jeoung, D Hye-Young; Chun, Ji-Eun

    2013-09-01

    Necrotic enteritis is an enteric disease of poultry resulting from infection by Clostridium perfringens with coinfection by Eimeria spp. constituting a major risk factor for disease pathogenesis. This study compared three commercial broiler chicken lines using an experimental model of necrotic enteritis. Day-old male Cobb, Ross, and Hubbard broilers were orally infected with viable C. perfringens and E. maxima and fed a high-protein diet to promote the development of experimental disease. Body weight loss, intestinal lesions, and serum antibody levels against alpha-toxin and necrotic enteritis B-like (NetB) toxin were measured as parameters of disease susceptibility and host immune response. Cobb chickens exhibited increased body weight loss compared with Ross and Hubbard breeds and greater gut lesion severity compared with Ross chickens. NetB antibody levels were greater in Cobb chickens compared with the Ross or Hubbard groups. These results suggest that Cobb chickens may be more susceptible to necrotic enteritis in the field compared with the Ross and Hubbard lines. PMID:24283139

  3. Design of high productivity antibody capture by protein A chromatography using an integrated experimental and modeling approach.

    OpenAIRE

    Ng, C. K.; Osuna-Sanchez, H.; Valéry, E.; Sørensen, E; Bracewell, D. G.

    2012-01-01

    An integrated experimental and modeling approach for the design of high productivity protein A chromatography is presented to maximize productivity in bioproduct manufacture. The approach consists of four steps: (1) small-scale experimentation, (2) model parameter estimation, (3) productivity optimization and (4) model validation with process verification. The integrated use of process experimentation and modeling enables fewer experiments to be performed, and thus minimizes the time and mate...

  4. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

    International Nuclear Information System (INIS)

    Here, we report a new and rapid radiosynthesis of 18F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([18F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [18F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [18F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18F-fluorodeoxyglucose ([18F]FDG). The fully automated radiosynthesis of [18F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [18F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [18F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [18F]FDG showed that both radiotracers were able to detect melanoma lesions, but [18F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [18F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  5. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [{sup 18}F]ICF01006, a highly promising melanoma PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Cachin, Florent [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Centre Jean Perrin, Clermont-Ferrand (France); Bonnet, Mathilde [U1071 INSERM-Universite d' Auvergne, M2USH, Clermont-Ferrand (France); Askienazy, Serge [CYCLOPHARMA Laboratories, Biopole Clermont-Limagne, Saint-Beauzire (France); Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France)

    2012-09-15

    Here, we report a new and rapid radiosynthesis of {sup 18}F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([{sup 18}F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [{sup 18}F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [{sup 18}F]ICF01006 were evaluated at different stages of tumoural growth and compared to {sup 18}F-fluorodeoxyglucose ([{sup 18}F]FDG). The fully automated radiosynthesis of [{sup 18}F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/{mu}mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [{sup 18}F]ICF01006 tumoural uptake of 1.64 {+-} 0.57, 3.40 {+-} 1.47 and 11.44 {+-} 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [{sup 18}F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 {+-} 2.08 %ID/g (versus 0.41 {+-} 0.90 %ID/g in control mice). In the two models, comparison with [{sup 18}F]FDG showed that both radiotracers were able to detect melanoma lesions, but [{sup 18}F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [{sup 18}F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  6. A novel bead-based assay to detect specific antibody responses against Toxoplasma gondii and Trichinella spiralis simultaneously in sera of experimentally infected swine

    Directory of Open Access Journals (Sweden)

    Bokken Gertie CAM

    2012-03-01

    Full Text Available Abstract Background A novel, bead-based flow cytometric assay was developed for simultaneous determination of antibody responses against Toxoplasma gondii and Trichinella spiralis in pig serum. This high throughput screening assay could be an alternative for well known indirect tests like ELISA. One of the advantages of a bead-based assay over ELISA is the possibility to determine multiple specific antibody responses per single sample run facilitated by a series of antigens coupled to identifiable bead-levels. Furthermore, inclusion of a non-coupled bead-level in the same run facilitates the determination of, and correction for non-specific binding. The performance of this bead-based assay was compared to one T. spiralis and three T. gondii ELISAs. For this purpose, sera from T. gondii and T. spiralis experimentally infected pigs were used. With the experimental infection status as gold standard, the area under the curve, Youden Index, sensitivity and specificity were determined through receiver operator curve analysis. Marginal homogeneity and inter-rater agreement between bead-based assay and ELISAs were evaluated using McNemar's Test and Cohen's kappa, respectively. Results Results indicated that the areas under the curve of the bead-based assay were 0.911 and 0.885 for T. gondii and T. spiralis, respectively, while that of the T. gondii ELISAs ranged between 0.837 and 0.930 and the T. spiralis ELISA was 0.879. Bead-based T. gondii assay had a sensitivity of 86% and specificity of 96%, while the ELISAs ranged between 64-84% and 93-99%, respectively. The bead-based T. spiralis assay had a sensitivity of 68% and specificity of 100% while the ELISA scored 72% and 95%, respectively. Marginal homogeneity was found between the T. gondii bead-based test and one of the T. gondii ELISAs. Moreover, in this test combination and between T. spiralis bead-based assay and respective ELISA, an excellent inter-rater agreement was found. When results of

  7. Detection of experimental infections with 99mTc-labeled monoclonal antibodies against TNF-α and interleukin-8

    International Nuclear Information System (INIS)

    This study was designed to assess monoclonal antibodies (MAbs) directed against tumor necrosis factor-α (TNF-α) (anti-TNF) or interleukin-8 (anti-IL-8) as radioactive agents for the detection of Staphylococcus aureus- or Klebsiella pneumoniae-infected thighs in mice. At 5 min (acute infection) or 20 h (established) post-infection, 20 μg of the 99mTc-labeled MAbs were injected. At various time intervals, the accumulation of the radiotracer in the infected thighs was assessed and expressed as a target-to-nontarget (T/NT) ratio. The binding of 99mTc-labeled MAbs to circulating mononuclear cells and granulocytes was quantitated 20 h after injection. The pharmacokinetics of the MAbs, in relation to the control agents 99mTc-labeled polyclonal human immunoglobulin (IgG) and a 99mTc-labeled nonspecific IgG1 MAb, were also studied. In acute infections, 99mTc-anti-TNF accumulated to a higher extent (p 99mTc-IgG and was higher at 0.25 h in K. pneumoniae-infected mice (p 99mTc-IgG. In established S. aureus and K. pneumoniae infections, 99mTc-anti-IL-8 detected the infection more intensely than 99mTc-IgG until 1 h after injection. In both S. aureus and K. pneumoniae infections, localization of sites of infection correlates (p 99mTc-labeled MAbs to granulocytes and mononuclear cells in both acute and established infections. It was concluded that 99mTc-labeled MAbs, directed against TNF-α and IL-8, accumulate in bacterial infections in mice to a higher extent than does 99mTc-IgG after infection and is related to the binding of the antibodies to blood leukocytes. With these 99mTc-labeled MAbs, information might be gained about the development of an infection

  8. Detection of experimental thrombi in rabbits with an 131I-labelled fibrin-specific monoclonal antibody

    International Nuclear Information System (INIS)

    The detection of thrombi in rabbits has been investigated with 131I-labelled DD-3B6/22, a monoclonal antibody (Mab) reactive at high affinity (Kd=2.68x10-10 M) with human D Dimer (DD). DD-3B6/22 bound well to both 'fresh' and 'aged' human clots in an in vitro assay but showed poor binding to rabbit clots. However, reactivity was restored to rabbit blood if it was seeded, before clotting, with human DD covalently coupled to Sepharose beads. Thus, a rabbit model was developed in which blood was allowed to clot around DD-Sepharose beads introduced into the jugular vein. Gamma camera imaging showed that intact 131I-labelled DD-3B6/22 localised to these clots within 24 h. Uptake at this time was 0.202%±0.012% injected dose per gram (%ID/g) compared with 0.086±0.018%ID/g after injection of control antibody. 131I-labelled F(ab')2 fragments of DD-3B6/22 allowed earlier scintigraphic detection of the clot which was evident 4 h after injection. Uptake in the clot at 24 h was 0.154±0.038% ID/g compared with 0.109±0.027% ID/g for a control F(ab')2. As antigen levels in the clot are estimated to be less than 300 μg DD, thus representing a very small human clot, the DD-3B6/22 Mab would appear to have a good potential for the sensitive detection of thrombi in a clinical setting. (orig.)

  9. Recombinant antibodies and tumor targeting

    OpenAIRE

    Sheikholvaezin, Ali

    2006-01-01

    Different antibody derived constructs are rapidly advancing as putative tools for treatment of malignant diseases. Antibody engineering has added significant new technologies to modify size, affinities, solubility, stability and biodistribution properties for immunoconjugates. In the present thesis, the aim was to increase our knowledge on how new recombinant antibodies could be tailored to optimize localization to experimental tumors in mice. One hybridoma, producing the monoclonal antibody ...

  10. Age-dependent differences in cytokine and antibody responses after experimental RSV infection in a bovine model

    DEFF Research Database (Denmark)

    Grell, S.N.; Riber, Ulla; Tjørnehøj, Kirsten;

    2005-01-01

    Respiratory syncytial virus (RSV) causes severe respiratory disease in both infants and calves. As in humans, bovine RSV (BRSV) infections are most severe in the first 6 months of life. In this study, experimental infection with BRSV was performed in calves aged 1-5, 9-16 or 32-37 weeks. Compared...

  11. Comparative experimental studies into radioimmunoscintigraphy using radioactive antibodies in animals with HeLa cell carcinomas and Yoshida sarcomas

    International Nuclear Information System (INIS)

    TPA-positive and TPA-negative tumour-bearing animal systems (HeLa cell carcinomas in RNU rats and Yoshida sarcomas in Wistar rats) were examined to show that the method of scanning can well be used to visualise tumour tissue. In this connection, further attempts were made to shed light on the specifity of immunoscintigraphy in the search for tumour tissue. 125-Iodine-anti-TPA was found to be a specific carcinoma-seeking substance. The amount of antibodies accumulating in the tumour was multiplied by previous intravenous treatment of test animals with unspecific immunoglobulin. In control studies using 125-iodine-immunoglobulin the site of the carcinomatous tissue could not be determined with sufficient diagnostic accuracy. It was found that the discriminating power of radioimmunoscintigraphy using 125-iodine-anti-TPA is quite unrelated to an increased circulation in the proliferating carcinomatous tissue. For the detection of TPA in HeLa cell carcinomas anti-TPA PAP stains were prepared. Radionuclide studies using 125-iodine-anti-TPA were also useful in the visualisation of the Yoshida sarcoma, even though this scores negative on TPA. Here, the amounts of radioactivity accumulating in the tumour were smaller than with the HeLa cell carcinoma. Moreover, peak levels were measured after no less than one day, as compared to the five days required for HeLa cell tumours to reach maximum levels. This finding would appear to provide presumptive evidence that there are other, unspecific mechanisms of tumour selectivity. (orig/MG)

  12. Evaluation of the Therapeutic Potential of Anti-TLR4-Antibody MTS510 in Experimental Stroke and Significance of Different Routes of Application

    Science.gov (United States)

    Czech-Zechmeister, Bozena; Könnecke, Birte; Lühder, Fred; Trendelenburg, George

    2016-01-01

    Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged. PMID:26849209

  13. Promises and Expectations

    OpenAIRE

    Florian Ederer; Alexander Stremitzer

    2014-01-01

    We investigate why people keep their promises in the absence of external enforcement mechanisms and reputational effects. In a controlled laboratory experiment we show that exogenous variation of second-order expectations (promisors' expectations about promisees' expectations that the promise will be kept) leads to a significant change in promisor behavior. We provide clean evidence that a promisor's aversion to disappointing a promisee's expectation leads her to keep her promise. We propose ...

  14. Treatment with anti-interferon-gamma monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice

    DEFF Research Database (Denmark)

    Espejo, C; Penkowa, M; Sáez-Torres, I;

    2001-01-01

    The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial. We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R......(-/-)) mouse types: C57Bl/6x129Sv, with a disruption of the IFN-gamma receptor cytoplasmic domain, and 129Sv, homozygous for a disrupted IFN-gamma receptor gene. Mice were immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. A subgroup of mice was treated with anti-IFN-gamma monoclonal...

  15. The Kalamazoo Promise Scholarship

    Science.gov (United States)

    Bartik, Timothy J.; Lachowska, Marta

    2014-01-01

    This study takes advantage of the unexpected announcement of the Kalamazoo Promise to study its effects on student achievement and behavior in high school. The Kalamazoo Promise provides college scholarships to graduates of Kalamazoo Public Schools (KPS), a midsized urban school district in Michigan that is racially and economically diverse.…

  16. Protective effects of chicken egg yolk antibody (IgY) against experimental Vibrio splendidus infection in the sea cucumber (Apostichopus japonicus).

    Science.gov (United States)

    Li, Xiaoyu; Jing, Kailin; Wang, Xitao; Li, Yuan; Zhang, Meixia; Li, Zhen; Xu, Le; Wang, Lili; Xu, Yongping

    2016-01-01

    Vibrio splendidus is one of the most harmful pathogens associated with skin ulceration syndrome in the sea cucumber (Apostichopus japonicus) due to its high virulence and frequency of appearance. The objective of this study was to determine the effectiveness of chicken egg yolk antibody (IgY) against V. splendidus infection in the sea cucumber. Whole V. splendidus cells were used as an immunogen to immunize 20 White Leghorn hens (25 weeks old). IgY was produced from egg yolks obtained from these immunized hens using water dilution, two-step salt precipitation and ultrafiltration. The purity of the IgY produced was approximately 83%. Enzyme-linked Immunosorbent Assay indicated a high specificity for IgY with a maximum antibody titer of 320,000. The growth of V. splendidus in liquid medium was significantly inhibited by IgY in a dose-dependent manner at concentrations ranging from 1 to 10 mg/mL. The protective effects of IgY were evaluated in sea cucumber by intraperitoneally injecting anti-V. splendidus IgY antibodies (10 mg/mL) or immersing the sea cucumber in aqueous IgY (1 g/L) after an intraperitoneal injection of V. splendidus. Intraperitoneal injection resulted in an 80% survival while immersion resulted in a 75% survival during the 11-day experimental period. The survival rates were significantly higher than the positive control and the non-specific IgY group (P < 0.05). As well, the bacterial burden in the respiratory tree, intestine and coelomic liquid was significantly (P < 0.05) lower in sea cucumber treated with specific IgY than those treated with non-specific IgY. The phagocytosis of coelomocytes for V. splendidus in the presence of specific IgY was significantly (P < 0.05) higher than that obtained with non-specific IgY or without IgY, suggesting that specific IgY enhanced phagocytic activity. The current work suggests that specific IgY has potential for protecting sea cucumbers against V. splendidus infection. PMID:26592708

  17. Mannan oligosaccharide increases serum concentrations of antibodies and inflammatory mediators in weanling pigs experimentally infected with porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Che, T M; Song, M; Liu, Y; Johnson, R W; Kelley, K W; Van Alstine, W G; Dawson, K A; Pettigrew, J E

    2012-08-01

    Mannan-containing products are capable of modulating immune responses in animals. However, different products may have diverse immunomodulation. The experiment was conducted to examine effects of mannan oligosaccharide (Actigen; ACT) on growth performance and serum concentrations of antibodies and inflammatory mediators in weanling pigs (Sus scrofa) experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV). A total of 32 PRRSV-negative pigs (3 wk old) were randomly assigned from within blocks to 1 of 4 treatments in a 2 by 2 factorial arrangement [2 types of diet: control (0%) and ACT addition (0.04%); and with and without PRRSV] in a randomized complete block design. Pigs were blocked by initial BW within sex. Ancestry was equalized across treatments. Pigs (8/treatment) were kept individually in each pen. After 2 wk of an 8-wk period of feeding the treatments, pigs received an intranasal inoculation of PRRSV or sham medium at 5 wk of age. Infection by PRRSV decreased ADG, ADFI, and G:F throughout the experiment (P infected pigs but not in sham controls (interaction, P = 0.009). Dietary ACT did not affect viremia in infected pigs (P > 0.05), but increased PRRSV-specific antibody titer at 35 DPI (P = 0.042). Infection with PRRSV induced the febrile responses of pigs from 3 to 10 DPI (P pigs was found slightly elevated by ACT (P = 0.045). Infected pigs had greater serum concentrations of IL-1β, tumor necrosis factor (TNF)-α, IL-12, interferon (IFN)-γ, IL-10, and haptoglobin (Hp) than sham controls (P serum TNF-α concentration regardless of PRRSV (P = 0.058). The ACT × PRRSV interaction was significant for IL-1β (P = 0.016), IL-12 (P = 0.026), and Hp (P = 0.047), suggesting that infected pigs fed ACT had greater serum concentrations of these mediators than those fed the control. The increases in IL-1β and IL-12 may favorably promote innate and T-cell immune functions in infected pigs fed ACT. Feeding ACT may be useful as ACT is

  18. Antithyroid microsomal antibody

    Science.gov (United States)

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked to an increased risk ...

  19. Characterization and evaluation of a novel anti-MUC-1 monoclonal antibody:induction of the idiotypic network in experimental mice

    Institute of Scientific and Technical Information of China (English)

    马洁; 曹利人

    2003-01-01

    Objective To investigate the anti-idiotypic effect induced by a monoclonal antibody.Methods A conventional fusion method was used to obtain hybridoma cells produing monoclonal antibody, which were detected by flow cytometry. ELISA were used to detect the humoral response induced by the antibody in mice. Cytotoxic and proliferation experiments were used to detect the cellular response induced by the antibody in mice.Results CS20 is a MUC-1 specific monoclonal antibody that strongly reacts with MUC-1 antigen expressed on the cell surface of breast cancer cells. The antibody could not kill tumor cells directly through complement-dependant cytotoxicity or antibody-dependant cell-mediated cytotoxicity. However, after 6 administrations of mAb CS20-KLH (keyhole limpet hemocyanin) conjugated to BALB/c mice (n=5) at a dose of 50 μg/mouse, anti-idiotypic antibodies and anti-anti-idiotypic antibodies were induced. T cells derived from CS20-KLH-immunized mice responded to mAb CS20, indicating the existence of idiotype-specific T cells.Conclusion These data indicated the possibility of using MUC-1 specific antibody for active immunotherapy of breast cancer.

  20. scFv from Antibody That Mimics gp43 Modulates the Cellular and Humoral Immune Responses during Experimental Paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Grasielle Pereira Jannuzzi

    Full Text Available Paracoccidioidomycosis (PCM, caused by Paracoccidioides species is a prevalent systemic and progressive mycosis that occurs in Latin America. It is caused by Paracoccidioides species. Immunization with dendritic cells transfected with a plasmid encoding the scFv (pMAC/PS-scFv that mimics the main antigen of P. brasiliensis (gp43 confers protection in experimental PCM. DCs link innate and adaptive immunity by recognizing invading pathogens and selecting the type of effector T cell to mediate the immune response. Here, we showed that DC-pMAC/PS-scFv induces the activation of CD4+ and CD8+ T cells. Moreover, our results demonstrated that BALB/c mice infected with P. brasiliensis and treated with DC-pMAC/PS-scFv showed the induction of specific IgG production against gp43 and IFN-γ, IL-12 and IL-4 cytokines. Analysis of regional lymph nodes revealed increases in the expression of clec7a, myd88, tlr2, gata3 and tbx21, which are involved in the immune response. Taken together, our results indicate that the scFv modulates the humoral and cellular immune responses and presents epitopes to CD4+ and CD8+ T cells.

  1. Malaria Vaccine Shows Promise in Small Study

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158765.html Malaria Vaccine Shows Promise in Small Study It protected ... TUESDAY, May 10, 2016 (HealthDay News) -- An experimental malaria vaccine protects a majority of adults against the ...

  2. New Dengue Virus Vaccine Shows Promise

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_157799.html New Dengue Virus Vaccine Shows Promise Research may also aid ... 16, 2016 (HealthDay News) -- An experimental vaccine against dengue -- the mosquito-borne virus behind a very painful ...

  3. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  4. Autologous antibodies that bind neuroblastoma cells.

    Science.gov (United States)

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies. PMID:26210205

  5. Promising More Information

    Science.gov (United States)

    2003-01-01

    When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.

  6. Is Bitcoin Promising?

    Institute of Scientific and Technical Information of China (English)

    张程程

    2014-01-01

    On 26th Feb. 2014, the biggest Bitcoin trading platform al over the world was of line. It was bankrupt due to data theft. Global Bitcoin players got into a panic. Is Bitcoin promising? Below I wil analyze this question on several aspects, which are Bitcoins’ traits, demerits, and contrasts.

  7. EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity

    OpenAIRE

    Olivier, Stéphane; Jacoby, Marine; Brillon, Cédric; Bouletreau, Sylvana; Mollet, Thomas; Nerriere, Olivier; Angel, Audrey; Danet, Sévérine; Souttou, Boussad; Guehenneux, Fabienne; Gauthier, Laurent; Berthomé, Mathilde; Vié, Henri; Beltraminelli, Nicola; Mehtali, Majid

    2010-01-01

    Monoclonal antibodies (mAbs) represent the fastest growing class of therapeutic proteins. The increasing demand for mAb manufacturing and the associated high production costs call for the pharmaceutical industry to improve its current production processes or develop more efficient alternative production platforms. The experimental control of IgG fucosylation to enhance antibody dependent cell cytotoxicity (ADCC) activity constitutes one of the promising strategies to improve the efficacy of m...

  8. Biodistribution and pharmacokinetics of monoclonal antibody T1h and variant anti-CD6 murine 10D12 in healthy animals and in experimental arthritis model

    International Nuclear Information System (INIS)

    Biodistribution and pharmacokinetic of two radio labeled monoclonal antibodies was performed with the help of imaging techniques. Isotopic labeling was carried out by means of standardized methods. Pharmacokinetic evaluation was performed using the population approach and sparse data design. Introduction: Targeted therapy with monoclonal antibodies (MAb) is an efficient option for the treatment of rheumatoid arthritis. Th1 is a MAb anti human CD6 developed for the treatment of autoimmune disease and 10D12 is its counterpart anti murine CD6 developed as a pharmacological tool to get deep into the response mechanisms in animals models of rheumatoid arthritis.To investigate the behavior of both antibodies in the assay system, molecules were labeled with 125I to evaluate pharmacokinetic in healthy animals and with 99mTc to evaluate the antibody uptake in inflamed area of induced arthritis. Materials and methods: Antibodies were supplied by the Center of Molecular immunology. Iodination was performed by the iodogen method and technetium labeling was carried out directly by Schwarz method. Female C57BL6 from CENPALAB were used for experiments. Biodistribution and pharmacokinetic was performed by a sparse data design using the population approach. Uptake in region of inflammation was quantified by gammagraphy at the same time points of blood sampling. A compartmental model was build to quantify uptake kinetic. Pharmacokinetic profiles were analyzed using MONOLIX software version 4.2. Results: Minor pharmacokinetic differences were found between monoclonal antibodies labeled with 125I and 99mTc. As a humanized antibody, T1h shows a faster clearance than 10D12 and a biodistribution pattern reflecting preference for excretion mechanisms. The arthritis accumulation was not consistent with a targeted mediated uptake. On the other hand, radio labeled 10D12 shows an accumulation profile in arthritis with two peaks of maximum concentration representing an initial transit to

  9. The promise of dialogue

    DEFF Research Database (Denmark)

    Phillips, Louise Jane

    three research traditions - dialogic communication theory, action research, and science and technology studies. It also provides an empirically rich account of the dialogic turn through case studies of how dialogue is enacted in the fields of planned communication, public engagement with science and...... in the fields in which it is practised and how can we analyse those practices in ways that take account of their complexities? The Promise of Dialogue presents a novel theoretical framework for analysing the dialogic turn in the production and communication of knowledge that builds bridges across...... collaborative research. A critical, reflexive approach is taken that interrogates the complexities, tensions and dilemmas inherent in the enactment of “dialogue” and is oriented towards further developing dialogic practices from a position normatively supportive of the dialogic turn....

  10. Influence of maternal antibodies on efficacy of porcine circovirus type 2 (PCV2) vaccination to protect pigs from experimental infection with PCV2

    OpenAIRE

    Opriessnig, T.; Patterson, A. R.; Halbur, P. G.; Elsener, J.; Meng, X.J.

    2008-01-01

    Due to the ubiquitous nature of porcine circovirus type 2 (PCV2) in the pig population and the increasing use of PCV2 vaccines in breeding herds, the majority of dams have been exposed to field PCV2 or PCV2 vaccines, resulting in piglets with varied levels of passively acquired PCV2 maternal antibodies. The objective of the current research was to investigate the influence of passively acquired anti-PCV2 antibodies on PCV2 vaccine efficacy. Sixty 26-day-old pigs were divided into four groups:...

  11. Influence of Maternal Antibodies on Efficacy of Porcine Circovirus Type 2 (PCV2) Vaccination To Protect Pigs from Experimental Infection with PCV2▿

    OpenAIRE

    Opriessnig, T.; Patterson, A. R.; Elsener, J.; Meng, X.J.; Halbur, P. G.

    2007-01-01

    Due to the ubiquitous nature of porcine circovirus type 2 (PCV2) in the pig population and the increasing use of PCV2 vaccines in breeding herds, the majority of dams have been exposed to field PCV2 or PCV2 vaccines, resulting in piglets with varied levels of passively acquired PCV2 maternal antibodies. The objective of the current research was to investigate the influence of passively acquired anti-PCV2 antibodies on PCV2 vaccine efficacy. Sixty 26-day-old pigs were divided into four groups:...

  12. The role of antibodies in myasthenia gravis.

    Science.gov (United States)

    De Baets, M; Stassen, M H W

    2002-10-15

    Myasthenia gravis is an autoimmune disease associated with antibodies directed to the postsynaptic acetylcholine receptor. These antibodies reduce the number of receptors. Autoantibodies against AChR and other muscle antigens can be used for the diagnosis of myasthenia gravis and related disorders. The origin and the role of these antibodies in the disease are discussed. Experimental autoimmune myasthenia gravis, an experimental model closely mimicking the disease, has provided answers to many questions about the role of antibodies, complement macrophages and AChR anchor proteins. Genetically modified anti-AChR antibodies may also be used in the future to treat myasthenia. PMID:12220686

  13. Promising treatments in development for food allergies.

    Science.gov (United States)

    Rancé, Fabienne

    2004-11-01

    Up to 6% of young children and 2% of adults suffer from food allergy. Among them many have IgE-mediated food allergy, a condition with potentially fatal allergic reactions. The only proven treatment is avoidance of the offending food, which can be identified using standardised allergic tests. However, several studies have addressed possible definite treatment options for food allergy. Immunotherapy, administered orally or by systemic injections, shows promising preliminary results, but these therapeutics are based on studies with insufficient scientific support, or are associated with a high risk of severe side effects. At present, no studies can support pharmacotherapy. However, promising results were recently published with anti-IgE antibodies in a human trial, and various approaches in a mouse model of food allergy (chinese herbal medicine, specific modulation of the T-cell response). Rapidly evolving findings might provide hope for a cure for food allergy in the near future. PMID:15571483

  14. Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society December 7-10, 2015, San Diego, CA, USA.

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M; Lund-Johansen, Fridtjof; Bradbury, Andrew R M; Carter, Paul J; Melis, Joost P M

    2016-01-01

    The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. PMID:26909869

  15. Application of Monoclonal Antibodies in Veterinary Parasitology

    Directory of Open Access Journals (Sweden)

    Gupta A.

    2011-08-01

    Full Text Available The discovery of hybridoma technology by Kohler and Milstein in 1975, heralded a new era in antibody research. Mouse hybridomas were the first reliable source of monoclonal antibodies. The generation of monoclonal antibodies from species other than rats and mice, has developed slowly over the last 30 years. The advent of antibody engineering and realization of the advantages of non murine antibodies has increased their relevance recently. However, in the area of veterinary parasitology, monoclonal antibodies are just beginning to fulfill the promises inherent in their great specificity for recognizing and selectively binding to antigens. This review describes the recent advances in the application of monoclonal antibodies for immunodiagnosis / prophylaxis and immunotherapy of parasitic diseases. [Vet. World 2011; 4(4.000: 183-188

  16. Treatment of leukemia with radiolabeled monoclonal antibodies.

    Science.gov (United States)

    Sgouros, G; Scheinberg, D A

    1993-01-01

    In contrast to radioimmunotherapy of solid disease, wherein the primary obstacle to success is access of radiolabeled antibody to antigen-positive cells, in the treatment of leukemia delivering a lethal absorbed dose to the isolated cell appears to be the primary obstacle. The isolated cell is defined as one that is exposed only to self-irradiation (from internalized or surface-bound radiolabeled antibody) and to irradiation from free antibody in the blood. It is isolated in the sense that the particulate (beta, electron, alpha) emissions from its nearest neighboring antigen-positive cell do not contribute to its absorbed dose. Disease in the bone marrow and other tissues, since it is confined to a smaller volume, is more easily eradicated because the absorbed dose to a given cell nucleus is enhanced by emissions from adjacent cells (a smaller fraction of the emission energy is 'wasted'). The optimization simulations presented above for the M195 antibody suggest that the optimum dose of antibody that should be administered is that required to yield a concentration within the distribution volume of the antibody that is approximately equal to the concentration of antigen sites as determined by the tumor burden. Although not specifically considered in the modeling example presented above, antibody internalization and catabolism may be expected to play an important role in radioimmunotherapy treatment planning of leukemia. Depending upon the kinetics of internalization and catabolism, the absorbed dose to the red marrow and to antigen-positive cells may be reduced considerably, since catabolism, assuming that it is followed by rapid extrusion of the radioactive label, would decrease the cells' exposure time considerably. The recently demonstrated effectiveness of radioimmunotherapy in certain cases of B-cell lymphoma and in reducing tumor burden in acute myelogenous leukemia suggests that radioimmunotherapy is beginning to fulfill the promise held when it was initially

  17. Antibody-Directed Phototherapy (ADP

    Directory of Open Access Journals (Sweden)

    M. Adil Butt

    2013-04-01

    Full Text Available Photodynamic therapy (PDT is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug and oxygen to generate cytotoxic oxygen species. These free radical species damage cellular components leading to cell death. Despite its benefits, the complexity, limited potency and side effects of PDT have led to poor general usage. However, the research area is very active with an increasing understanding of PDT-related cell biology, photophysics and significant progress in molecular targeting of disease. Monoclonal antibody therapy is maturing and the next wave of antibody therapies includes antibody-drug conjugates (ADCs, which promise to be more potent and curable. These developments could lift antibody-directed phototherapy (ADP to success. ADP promises to increase specificity and potency and improve drug pharmacokinetics, thus delivering better PDT drugs whilst retaining its other benefits. Whole antibody conjugates with first generation ADP-drugs displayed problems with aggregation, poor pharmacokinetics and loss of immuno-reactivity. However, these early ADP-drugs still showed improved selectivity and potency. Improved PS-drug chemistry and a variety of conjugation strategies have led to improved ADP-drugs with retained antibody and PS-drug function. More recently, recombinant antibody fragments have been used to deliver ADP-drugs with superior drug loading, more favourable pharmacokinetics, enhanced potency and target cell selectivity. These improvements offer a promise of better quality PDT drugs.

  18. Bispecific antibodies.

    Science.gov (United States)

    Kontermann, Roland E; Brinkmann, Ulrich

    2015-07-01

    Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also place targets into close proximity, either to support protein complex formation on one cell, or to trigger contacts between cells. Examples of 'forced-connection' functionalities are bsAbs that support protein complexation in the clotting cascade, or tumor-targeted immune cell recruiters and/or activators. Following years of research and development (R&D), the first bsAb was approved in 2009. Another bsAb entered the market in December 2014 and several more are in clinical trials. Here, we describe the potentials of bsAbs to become the next wave of antibody-based therapies, focusing on molecules in clinical development. PMID:25728220

  19. Experimental and In Silico Modelling Analyses of the Gene Expression Pathway for Recombinant Antibody and By-Product Production in NS0 Cell Lines

    OpenAIRE

    Emma J Mead; Lesley M Chiverton; Sarah K Spurgeon; Martin, Elaine B.; Montague, Gary A.; C Mark Smales; Tobias von der Haar

    2012-01-01

    Monoclonal antibodies are commercially important, high value biotherapeutic drugs used in the treatment of a variety of diseases. These complex molecules consist of two heavy chain and two light chain polypeptides covalently linked by disulphide bonds. They are usually expressed as recombinant proteins from cultured mammalian cells, which are capable of correctly modifying, folding and assembling the polypeptide chains into the native quaternary structure. Such recombinant cell lines often va...

  20. Effects of experimental immunosuppression in cattle with persistently high antibody levels to Salmonella Dublin lipopolysaccharide O-antigens

    OpenAIRE

    Nielsen Liza R; Jensen Asger L; Agerholm Jørgen S; Lomborg Sanne R

    2007-01-01

    Abstract Background Salmonella Dublin (S. Dublin) is a zoonotic bacterium which is host adapted to cattle. The bacterium can cause subclinical persistent infection in cattle (carriers), which may be reactivated. During reactivation, animals may shed bacteria, thus constituting a source of infection for other animals. Identification of such carriers is assumed to be critical in attempts to control and eradicate the infection. Some authors suggest that persistently high antibody levels in serum...

  1. Single-domain antibodies for biomedical applications.

    Science.gov (United States)

    Krah, Simon; Schröter, Christian; Zielonka, Stefan; Empting, Martin; Valldorf, Bernhard; Kolmar, Harald

    2016-02-01

    Single-domain antibodies are the smallest antigen-binding units of antibodies, consisting either only of one variable domain or one engineered constant domain that solely facilitates target binding. This class of antibody derivatives comprises naturally occurring variable domains derived from camelids and sharks as well as engineered human variable or constant antibody domains of the heavy or light chain. Because of their high affinity and specificity as well as stability, small size and benefit of multiple re-formatting opportunities, those molecules emerged as promising candidates for biomedical applications and some of these entities have already proven to be successful in clinical development. PMID:26551147

  2. Cell-Free Synthesis Meets Antibody Production: A Review

    OpenAIRE

    Marlitt Stech; Stefan Kubick

    2015-01-01

    Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG) molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv) and antigen binding fragments (Fab), have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufactu...

  3. Experimental on Antibody Targeting Liver Cancer Stem Cell Treatment%肝癌干细胞抗体靶向治疗的实验

    Institute of Scientific and Technical Information of China (English)

    孙力超; 赵璇; 孙立新; 遇珑; 杨治华; 冉宇靓

    2011-01-01

    Objective To study the biological characteristics and function of the anti- hepatocellular carcinoma cancer stem cells (HCC-CSC) monoclonal antibody 15B7 in vivo and in vitro, and to investigate whether the targeting liver stem cells can inhibit recurrence, spontaneous lung metastasis and prolong the survival of tumor-bearing mice. Methods Monoclonal antibody 15B7 which could recognize HCC-CSC was identified by two-color immunofluorescence, two-color flow cytometry and subcutaneous tumor formation assay. CD133+ phenotype cells were sorted from BEL7402 cell lines by the flow cytometry and cultured in serum free medium. The function of 15B7 was identified by CCK8 cell proliferation, invasion assay, migration assay and flow cytometry. The inhibition of implanted tumor growth and spontaneous lung metastasis of monoclonal antibody 15B7 were studied by tumor treatment experiments and the survival of mice was also observed. The antigen of 15B7 was identified by western blotting. Results The results of two-color immunofluorescence and two-color flow cytometry showed that monoclonal antibody 15B7 could recognized cells which also were partly co-stained with ESA or CD133. 15B7+ or ESA+ cells or CD133+ cells sorted by flow cytometry could form mammospheres after serum-free suspension culture. 1 × 104 15B7+ cells were inoculated into the nude mice and developed visible tumors in 2 months. In vitro functional experiments showed that monoclonal antibody 15B7 could inhibit the proliferation, migration and invasion of CD133+ cells, and the inhibition rates was 13. 8%, 15. 7% and 30. 9%, respectively. Furthermore, CD133+ cells incubated with monoclonal antibody 15B7 were induced G1 phase arrest.Animal experiment revealed that monoclonal antibody 15B7 significantly inhibited tumor growth by 60. 5%. Conclusion 15B7 not only inhibited tumor growth. The results indicated that targeting cancer stem cell antibody therapy had significant advantages and monoclonal antibody 15B7

  4. Radioimmunoimaging of experimental thrombi in dogs using Tc-99m labeled monoclonal antibody fragments [MAPab-F(ab')/sub 2/] reactive with human platelets

    International Nuclear Information System (INIS)

    Radioimmunoimaging of thrombi could have great clinical value in the management of coronary artery and thromboembolic disease. In-111-oxine-labeled platelets currently used require platelet isolation, delayed imaging, background subtraction and there is also potential for damaging or contaminating platelets during labeling. Murine monoclonal antibody (IgG/sub 2/a) fragments directed against human platelet membrane components (cross-reactive with dog platelets) were labeled with Tc-99m and repurified from ''kits''. After radiolabeling, 91.5-93.3% of the Tc-99m was antibody-associated. The preparations retained immunoreactivity, as determined by the ratio of cell to plasma-associated radioactivity (ratios 54.7-63.8). Tc-99m-MAPAb-F(ab')/sub 2/ were injected i.v. into dogs with thrombi produced in peripheral and pulmonary veins and arteries. About 50% of the radioactivity was cleared from the blood in 3-6 min. and 18-24% was excreted in the urine within 3 hrs. The thrombi were consistently and easily visible within 1-3 hrs. with no need for blood pool subtraction. In some cases, intimal damage along the path of catheters was seen. No adverse side effects were observed. The advantages of this method are: short and simple preparation, no need for blood pool subtraction and early visualization of thrombi. Human studies are warranted to determine its clinical efficacy

  5. Monoclonal antibodies

    International Nuclear Information System (INIS)

    Monoclonal antibodies (MAbs) are antibodies having single specificity for a given antigen site (epitope). The development of hybridoma technology and the relative ease by which MAbs can be prepared has revolutionized many aspects of serological applications in diagnosis and differentiation of disease producing agents. The property of monospecificity offers advantages in diagnostic applications over polyclonal sera in that tests can be defined exactly with regard to the antigen detected and the affinity of reaction between the given antigenic site and the monoclonal reagent. In addition, MAbs offer better possibilities for test standardization, because the same reagent can be used in different laboratories. Such an MAb can be supplied by a central laboratory or 'grown' from hybridoma cells, ensuring that the resultant product is identical from laboratory to laboratory and that the part of the test involving the MAb reaction is the same. The methodologies for inoculation regimes, mice, cloning methods, selection of fusion partners, etc., have been validated extensively in developed country laboratories. The decision to establish a MAb production facility must be examined on a strict cost-benefit basis, since it is still expensive to produce a product. There are many MAbs available that should be sought to allow exploitation in developing tests. If a production facility is envisaged, it should produce reagents for national needs, i.e. there should be a clear problem oriented approach whereby exact needs are defined. In the field of veterinary applications, MAbs are the central reagent in many immunoassays based on the enzyme linked immunosorbent assay (ELISA). The development of specific tests for diagnosing diseases is dominated by MAbs and has been fuelled by a strong research base, mainly in developed countries allied to developing countries through the study of related diseases. Thus, there are very many assays dependent on MAbs, some of which form the basis of

  6. Milk supplemented with immune colostrum: protection against rotavirus diarrhea and modulatory effect on the systemic and mucosal antibody responses in calves experimentally challenged with bovine rotavirus.

    Science.gov (United States)

    Parreño, V; Marcoppido, G; Vega, C; Garaicoechea, L; Rodriguez, D; Saif, L; Fernández, F

    2010-07-01

    Group A bovine rotavirus (BRV) is the major cause of neonatal calf diarrhea worldwide. As a preventive strategy, we evaluated the protection and immunomodulation in two groups of BRV-inoculated calves. All calves received control colostrum (CC; VN=65,536; IgG(1)=16,384) prior to gut closure followed by the milk supplemented with immune colostrum (VN=1,048,576; IgG(1)=262,144), twice a day, for 14 days. Calves received milk supplemented with 0.8% immune colostrum [(Gp 1) VN=16,384; IgG(1)=4096] or milk supplemented with 0.4% immune colostrum [(Gp 2) VN=1024; IgG(1)=1024]. Calves receiving CC or colostrum deprived calves (CD) fed antibody (Ab) free milk served as controls (Gp 3 and 4). Calves were inoculated with virulent BRV IND at 2 days of age. Group 1 calves (milk IgG(1) 4096) showed 80% protection against BRV diarrhea and significantly reduced virus shedding. At 21 post-inoculation days (PID), the antibody secreting cell (ASC) responses of Gp 1 calves were limited mainly to duodenal and jejunal lamina propria (LP) with limited or no responses in systemic sites (spleen and PBL) and mesenteric lymph nodes. The profile of serum and fecal Ab responses as well as the ASC responses was also modulated by the presence of passive IgG(1) Abs and probably other colostrum components, toward higher titers of IgA Ab in serum and feces and a greater number of IgA ASC in the proximal intestine, reflecting positive modulation by colostrum toward this isotype associated with optimal protection of the intestinal mucosa. After challenge, at PID 21, all calves in Gp 1 and 2 were fully protected against diarrhea and only 1 of 5 calves in Gp 1 shed virus asymptomatically, indicating that the passive Ab treatment for 14 days was effective in protecting most of the animals after a first and a second virus exposure. The final outcome was a positive modulation of the mucosal immune responses and a high protection rate against diarrhea and virus shedding during the period of peak

  7. The antibody Hijikata Tatsumi

    Directory of Open Access Journals (Sweden)

    Éden Peretta

    2012-11-01

    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.

  8. Monoclonal antibodies.

    Science.gov (United States)

    2009-01-01

    The ability to produce and exploit monoclonal antibodies (mAbs) has revolutionized many areas of biological sciences. The unique property of an mAb is that it is a single species of immunoglobulin (IG) molecule. This means that the specificity of the interaction of the paratopes on the IG, with the epitopes on an antigenic target, is the same on every molecule. This property can be used to great benefit in immunoassays to provide tests of defined specificity and sensitivity, which improve the possibilities of standardization. The performance of assays can often be determined relating the actual weight of antibody (hence the number of molecules) to the activity. Often the production of an mAb against a specific epitope is the only way that biological entities can be differentiated. This chapter outlines the areas involving the development of assays based on mAbs. The problems involved address include the physical aspects of mAbs and how they may affect assay design and also the implications of results based on monospecific reagents. Often these are not fully understood, leading to assays that are less than satisfactory, which does not justify the relatively high cost of preparing and screening of mAbs. There are many textbooks and reviews dealing with the preparation of mAbs, the principles involved, and various purification and manipulative methods for the preparation of fragments and conjugation. There has been little general information attempting to summarize the best approaches to assay design using mAbs. Much time can be wasted through bad planning, and this is particularly relevant to mAbs. A proper understanding of some basic principles is essential. It is beyond the scope of this chapter to discuss all aspects, but major areas are highlighted. PMID:19219589

  9. Trichinella spiralis, T-britovi, and T-nativa: infectivity, larval distribution in muscle, and antibody response after experimental infection of pigs

    DEFF Research Database (Denmark)

    Kapel, C.M.O.; Webster, P.; Lind, Peter;

    1998-01-01

    The infectivity of Trichinella spiralis, T. nativa, and T. britovi was experimentally compared in pigs. Blood sampling was performed weekly, and muscle juices were obtained at slaughter 10 weeks after inoculation. Muscle larvae were found in all of four pigs inoculated with T. spiralis [mean 190...

  10. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  11. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1992-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

  12. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  13. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated

  14. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated

  15. An experimental study on labeling monoclonal antibody 4E5 with 131I and the lethal effects of 131I-4E5 against B cell lymphoma

    International Nuclear Information System (INIS)

    Objective: To label the monoclonal antibody 4E5 with 131I and to evaluate the lethal effects of 131I-4E5 against B cell lymphoma. Methods: 4E5 was radiolabeled with 131I using the Iodogen method at room temperature. The labeling efficiency and radiochemical purity was measured with trichloroacetic acid (TCA) precipitation, and the immune activity and stability of 131I-4E5 was analyzed. The lethal effects of 131I-4E5 and 4E5 against Raji cells were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny-lte-trazolium bromide (MTT) assay. Analysis of variance and t-test were used for data analysis with SPSS 13.0. Results: The labeling rate of 131I-4E5 was (78.3±2.4)%, and the radiochemical purity was (95.7±1.8)%. Its specific activity and radioactive concentration were 0.58 MBq/μg and 3.90 × 1010 Bq/L, respectively. The radiochemical purity of 131I-4E5 mixed with serum and PBS was over 90% after three days. The maximum specific binding efficiency of 131I-4E5 with Raji cells was (36.06±2.63)%. 131I-4E5 exhibited a dose-dependent cytotoxicity against Raji cells. The lethal effect of the high dose group was significantly stronger than that of the low dose group. When the radioactive concentrations were 1.48 × 1010, 7.40 × 109, 3.70 × 109, 1.85 × 109 and 9.25 × 108 Bq/L, the cell inhibition ratios were (52.98±5.19)%, (46.29±2.80)%, (41.05±4.83)%, (33.68±3.79)% and (17.89±2.78)%, respectively (F=33.882, P<0.001). In the 4E5 group, when concentrations of 4E5 were 20.0, 10.0, 5.0, 2.5 and 1.25 mg/L, the cell inhibition ratios were (32.98±3.99)%,(30.88±3.98)%, (27.14±2.05)%, (20.35±4.38)% and (8.42±1.05)%, respectively. Accordingly,significantly higher growth inhibition rates for Raji cells than 4E5 at all antibody concentrations were tested (t=5.290, 5.489, 4.596, 3.986 and 5.515, all P<0.05). Conclusions: The labeling efficiency and radiochemical purity of 131I-4E5 using Iodogen method is high,and the in vitro stability of 131I-4E5 is optimal. 131I-4E5

  16. Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity.

    OpenAIRE

    Cole, K S; Rowles, J L; Jagerski, B A; Murphey-Corb, M; Unangst, T; Clements, J E; Robinson, J.; Wyand, M S; Desrosiers, R C; Montelaro, R C

    1997-01-01

    Previous studies of attenuated simian immunodeficiency virus (SIV) vaccines in rhesus macaques have demonstrated the development of broad protection against experimental challenge, indicating the potential for the production of highly effective immune responses to SIV antigens. However, the development of this protective immune status was found to be critically dependent on the length of time postvaccination with the attenuated virus strain, suggesting a necessary maturation of immune respons...

  17. Antibody engineering & therapeutics, the annual meeting of the antibody society December 7–10, 2015, San Diego, CA, USA

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M.; Lund-Johansen, Fridtjof; Bradbury, Andrew R.M.; Carter, Paul J.; Melis, Joost P.M.

    2016-01-01

    ABSTRACT The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6–10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on “Antibodies to watch” in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. PMID:26909869

  18. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies are...... powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors such as......, including solid-phase peptide-carrier conjugation and peptide-carrier conjugation in solution. Upon immunization, adjuvants such as Al(OH)(3) are added together with the immunogenic peptide-carrier conjugate, which usually leads to high-titred antisera. Following immunization and peptide antibody...

  19. Mastering JavaScript promises

    CERN Document Server

    Hussain, Muzzamil

    2015-01-01

    This book is for all the software and web engineers wanting to apply the promises paradigm to their next project and get the best outcome from it. This book also acts as a reference for the engineers who are already using promises in their projects and want to improve their current knowledge to reach the next level. To get the most benefit from this book, you should know basic programming concepts, have a familiarity with JavaScript, and a good understanding of HTML.

  20. 不孕相关抗体检测女性不孕症的实验研究%Experimental study on infertility related antibody detection in female infertility

    Institute of Scientific and Technical Information of China (English)

    邓世英; 石姜; 聂红

    2014-01-01

    Objective To study whether the correlation exists between 6 kinds of autoimmune antibodies and female infertility . Methods The protein microarray technique was adopted to detect serum antibodies of anti-sperm antibodies(ASAb) ,anti-endome-trial(AEmAb) ,anti-zona pellucida(AZpAb) ,anti-ovarian(AVoAb) ,anti-hCG(AhCG Ab) and anti-trophoblastic(ATAb) in 140 ca-ses of female infertility and the correlation between these 6 kinds of antibody with female infertility was evaluated .Results Com-pared with the control group ,except AvoAb ,the positive rates of other 5 kinds of antibody had statistically significant differences (P0 .05) .The positive rate of ANA had no statistical difference between the infertility group and the control group (P>0 .05) ,but the titers of ANA in the experimenter were ≥1∶100(6/7) and most of karyotypes were nuclear coarse (5/7) ,which was differed from the low positive titer in the control group .The positive rate of ANA had statistical difference between the infertility related antibody positive and the infertility related antibody negative in the infertility patients .Conclusion ASAb ,AZpAb AEmAb , AhCGAb and ATAb are related with female sterility .The combined detection of these 6 kinds of antibody can significantly increase the detection sensitivity .%目的:探讨6种自身免疫抗体与女性不孕症间是否存在相关性。方法采用蛋白微阵列技术联合检测140例不孕症患者血清中抗精子抗体(ASAb)、抗子宫内膜抗体(AEmAb)、抗卵巢抗体(AVoAb)、抗透明带抗体(AZpAb)、抗滋养层抗体(ATAb)和抗人绒毛膜促性腺激素抗体(AhCG Ab),并评价这6种抗体与女性不孕症的相关性。结果与对照组相比,不孕组中除AVoAb外,其他5种抗体检测的阳性率比较差异有统计学意义(P<0.05)。不孕组中,6种抗体联合检测的阳性率与单独检测比较差异有统计学意义(P<0.05)。原发

  1. A promising therapeutic approach for multiple sclerosis: recombinant T-cell receptor ligands modulate experimental autoimmune encephalomyelitis by reducing interleukin-17 production and inhibiting migration of encephalitogenic cells into the CNS.

    Science.gov (United States)

    Sinha, Sushmita; Subramanian, Sandhya; Proctor, Thomas M; Kaler, Laurie J; Grafe, Marjorie; Dahan, Rony; Huan, Jianya; Vandenbark, Arthur A; Burrows, Gregory G; Offner, Halina

    2007-11-14

    Recombinant T-cell receptor ligands (RTLs) can prevent and reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). To evaluate regulatory mechanisms, we designed and tested RTL551, containing the alpha1 and beta1 domains of the I-A(b) class II molecule covalently linked to the encephalitogenic MOG-35-55 peptide in C57BL/6 mice. Treatment of active or passive EAE with RTL551 after disease onset significantly reduced clinical signs and spinal cord lesions. Moreover, RTL551 treatment strongly and selectively reduced secretion of interleukin-17 and tumor necrosis factor alpha by transferred green fluorescent protein-positive (GFP+) MOG-35-55-reactive T-cells and almost completely abrogated existent GFP+ cellular infiltrates in affected spinal cord sections. Reduced inflammation in spinal cords of RTL551-treated mice was accompanied by a highly significant downregulation of chemokines and their receptors and inhibition of VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) expression by endothelial cells. Thus, RTL therapy cannot only inhibit systemic production of encephalitogenic cytokines by the targeted myelin oligodendrocyte glycoprotein-reactive T-cells but also impedes downstream local recruitment and retention of inflammatory cells in the CNS. These findings indicate that targeted immunotherapy of antigen-specific T-cells can result in a reversal of CNS lesion formation and lend strong support to the application of the RTL approach for therapy in MS. PMID:18003831

  2. Is Technology Fulfilling Its Promise?

    Science.gov (United States)

    Weinstein, Margery

    2011-01-01

    Technology has promised trainers so much--from the ability to train distant learners to new ways of keeping young employees engaged. But has it delivered? In this article, several trainers consider whether their investment in training technology has been worth it.

  3. Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing

    OpenAIRE

    Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

    2013-01-01

    High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel ...

  4. The Promise of Quantum Simulation

    CERN Document Server

    Muller, Richard P

    2015-01-01

    Quantum simulation promises to be one of the primary application of quantum computers, should one be constructed. This article briefly summarizes the history quantum simulation in light of the recent result of Wang and coworkers demonstrating calculation of the ground and excited states for a HeH+ molecule, and concludes with a discussion of why this and other recent progress in the field suggests that quantum simulation of quantum chemistry has a bright future.

  5. Breaking promises. The Hungarian experience

    OpenAIRE

    Kornai, János

    2016-01-01

    My main aim is to present the phenomena related to fulfilment and breach of promises and the economic, political and ethical problems arising from these. I discuss questions that we all meet with in daily life and see mentioned in the press, other forums of public discourse, gatherings of friends, or sessions of Parliament. There are some who complain that a building contractor has not done a renovation job properly according to contract. Economists argue over the outcome of late repayment...

  6. The Promise of Quantum Simulation.

    Science.gov (United States)

    Muller, Richard P; Blume-Kohout, Robin

    2015-08-25

    Quantum simulations promise to be one of the primary applications of quantum computers, should one be constructed. This article briefly summarizes the history of quantum simulation in light of the recent result of Wang and co-workers, demonstrating calculation of the ground and excited states for a HeH(+) molecule, and concludes with a discussion of why this and other recent progress in the field suggest that quantum simulations of quantum chemistry have a bright future. PMID:26197037

  7. Nuclear energy: obstacles and promises

    International Nuclear Information System (INIS)

    Nuclear energy has distinctive merits (sustainable resources, low costs, no greenhouse gases) but its development must overcome serious hurdles (fear of accidents, radio-phobia, waste management). The large unit size of present-day reactors is compatible only with large electrical grids, and involves a high capital cost. Taking into account these different factors, the paper outlines how nuclear energy may contribute to the reduction of greenhouse gases, and which are the most promising developments. (author)

  8. Deep sequencing and human antibody repertoire analysis.

    Science.gov (United States)

    Boyd, Scott D; Crowe, James E

    2016-06-01

    In the past decade, high-throughput DNA sequencing (HTS) methods and improved approaches for isolating antigen-specific B cells and their antibody genes have been applied in many areas of human immunology. This work has greatly increased our understanding of human antibody repertoires and the specific clones responsible for protective immunity or immune-mediated pathogenesis. Although the principles underlying selection of individual B cell clones in the intact immune system are still under investigation, the combination of more powerful genetic tracking of antibody lineage development and functional testing of the encoded proteins promises to transform therapeutic antibody discovery and optimization. Here, we highlight recent advances in this fast-moving field. PMID:27065089

  9. Promising Rabies Vaccine for Postexposure Prophylaxis in Developing Countries, a Purified Vero Cell Vaccine Produced in China▿

    OpenAIRE

    Wang, Chuanlin; Zhang, Xiaowei; Song, Qingkun; Tang, Kun

    2010-01-01

    We evaluated the immunogenicity, safety, and antibody persistence of a Vero cell rabies vaccine manufactured in China, compared with those of Verorab. Adequate titers of antibody were observed for the two vaccines. ChengDa rabies vaccine could be a promising alternative vaccine for many developing countries which cannot afford expensive rabies vaccines.

  10. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit. PMID:26250412

  11. Trends in Malignant Glioma Monoclonal Antibody Therapy

    Science.gov (United States)

    Chekhonin, Ivan; Gurina, Olga

    2015-01-01

    Although new passive and active immunotherapy methods are emerging, unconjugated monoclonal antibodies remain the only kind of biological preparations approved for high-grade glioma therapy in clinical practice. In this review, we combine clinical and experimental data discussion. As antiangiogenic therapy is the standard of care for recurrent glioblastoma multiforme (GBM), we analyze major clinical trials and possible therapeutic combinations of bevacizumab, the most common monoclonal antibody to vascular endothelial growth factor (VEGF). Another humanized antibody to gain recognition in GBM is epidermal growth factor (EGFR) antagonist nimotuzumab. Other antigens (VEGF receptor, platelet-derived growth factor receptor, hepatocyte growth factor and c-Met system) showed significance in gliomas and were used to create monoclonal antibodies applied in different malignant tumors. We assess the role of genetic markers (isocitrate dehydrogenase, O6-methylguanine-DNA methyltransnsferase) in GBM treatment outcome prediction. Besides antibodies studied in clinical trials, we focus on perspective targets and briefly list other means of passive immunotherapy.

  12. Chitin fulfilling a biomaterials promise

    CERN Document Server

    Khor, Eugene

    2001-01-01

    The second edition of Chitin underscores the important factors for standardizing chitin processing and characterization. It captures the essential interplay between chitin's assets and limitations as a biomaterial, placing the past promises of chitin in perspective, addressing its present realities and offering insight into what is required to realize chitin's destiny (including its derivative, chitosan) as a biomaterial of the twenty-first century. This book is an ideal guide for both industrialists and researchers with a vested interest in commercializing chitin.An upd

  13. Antiphospholipid Antibody Syndrome

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  14. The antibody mining toolbox

    OpenAIRE

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D.; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba

    2013-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput ...

  15. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud;

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  16. Hepatitis A virus antibody

    International Nuclear Information System (INIS)

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  17. That’s a Promise

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The Internet has become a new platform to see if people are as good as their word WHEN Fu Weigang made a promise on his microblog at weibo.com to give 1 yuan($0.15) to the son of Zhang Miao,a young mother stabbed to death by a student in Xi’an last year,every time his post was forwarded,he never dreamed it would make such a public impact. The killer was sentenced to death and ordered to pay compensation of 45,498.50 yuan ($6,975) to Zhang’s family.Fu,a 34-year-old lawyer who works at the Shanghai Institute of

  18. Basic immunology of antibody targeted radiotherapy

    International Nuclear Information System (INIS)

    Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy

  19. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111In, 67Ga and 131I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  20. Monoclonal antibodies in animal production; their use in diagnostics and passive immunization.

    OpenAIRE

    Booman, P.

    1989-01-01

    One of the landmarks in immunology was the invention and development of monoclonal antibody-secreting hybridomas by Milstein and his coworkers. The enormous promise of monoclonal antibody technology, which became apparent soon after its discovery, may explain the unusual speed with which monoclonal antibodies have been applied to biological and medical sciences.In animal production monoclonal antibodies are increasingly finding application in the areas of diagnostics, passive immunization and...

  1. Antibody engineering: facing new challenges in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Laura SANZ; (A)ngel M CUESTA; Marta COMPTE; Luis (A)LVAREZ-VALLINA

    2005-01-01

    Antibody-based therapeutics are beginning to realize the promise enclosed in their early denomination as "magic bullets". Initial disappointment has turned into clinical and commercial success, and engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials. Recent structural and functional data have allowed the design of a new generation of therapeutic antibodies, with strategies ranging from complement-mediated and antibody-dependant cellular cytotoxicity enhancement to improved cytotoxic payloads using toxins, drugs,radionucleids and viral delivery. This review considers the structure of different types of recombinant antibodies, their mechanism of action and how their efficacy has been increased using a broad array of approaches. We will also focus on the additional benefits offered by the use of gene therapy methods for the in vivo production of therapeutic antibodies.

  2. International Collaboration: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    R. Jay Widmer

    2015-04-01

    Full Text Available Rambam Maimonides Medical Journal 2015 April; 6(2: e0012. ISSN: 2076-9172 Published online 2015 April 29. Special Issue on the Rambam-Mayo Collaboration Guest Editor: John H. Davidson, M.D., M.A.H.L. doi: 10.5041/RMMJ.10196. International Collaboration: Promises and Challenges R. Jay Widmer, M.D., Ph.D.,1 Jocelyn M. Widmer, Ph.D., M.P.H.,2 and Amir Lerman, M.D.1* 1Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and College of Medicine, Rochester, MN, USA; 2Department of Urban and Regional Planning, College of Design, Construction and Planning, University of Florida, Gainesville, FL, USA Conflict of interest: No potential conflict of interest relevant to this article was reported. * To whom correspondence should be addressed. E-mail: lerman.amir@mayo.edu Copyright: © 2015 Widmer et al. This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract We currently face a myriad of grand global challenges in fields such as poverty, the environment, education, science, and medicine. However, our current means of dealing with such challenges has fallen short, and ingenious solutions are required to overcome the inherent resistance to progress toward ameliorating such difficulties. Here, we highlight the promises and challenges of international collaboration in achieving success toward these trials. We note prior successes in fields such as education, medicine, science, and environmental issues made to date, yet at the same time we do note deficiencies and shortcomings in these efforts. Hence, the notion of international collaboration should be strengthened and encouraged by governments, non-profit organizations, and others moving forward using creative

  3. The Ambivalence of Promising Technology.

    Science.gov (United States)

    Shelley-Egan, Clare

    2010-08-01

    Issues of responsibility in the world of nanotechnology are becoming explicit with the emergence of a discourse on 'responsible development' of nanoscience and nanotechnologies. Much of this discourse centres on the ambivalences of nanotechnology and of promising technology in general. Actors must find means of dealing with these ambivalences. Actors' actions and responses to ambivalence are shaped by their position and context, along with strategic games they are involved in, together with other actors. A number of interviews were conducted with industrial actors with the aim of uncovering their ethical stances towards responsible development of nanotechnology. The data shows that standard repertoires of justification of nanotechnological development were used. Thus, the industrial actors fell back on their position and associated responsibilities. Such responses reinforce a division of moral labour in which industrial actors and scientists can focus on the progress of science and technology, while other actors, such as NGOs, are expected to take care of broader considerations, such as ethical and social issues. PMID:20835398

  4. Promising new cryogenic seal candidate

    International Nuclear Information System (INIS)

    Of the five seal candidates considered for the main propellant system of the Space Shuttle, only one candidate, the fluoroplastic Halar, satisfied all tests including the critical LO2 impact test and the cryogenic compression sealability test. Radiation-cross-linked Halar is a tough, strong thermoplastic that not only endured one hundred 2200 N compression cycles at 83 K while mounted in a standard military O-ring gland without cracking or deforming, but improved in sealability as a result of this cycling. Although these Halar O-rings require much higher sealing forces (approximately 500 N) at room temperature than rubber O-rings, on cooling to cryogenic temperatures the required sealing force only doubles, whereas the sealing force for rubber O-rings increases eightfold. Although these Halar O-rings were inadequately cross-linked, they still exhibited promise as LO2-compatible cryogenic seals. It is expected that their high-temperature properties can be greatly improved by higher degrees of cross-linking (e.g., by 20 mrad of radiation) without compromising their already excellent low-temperature properties. A direct comparison should then be obtained between the best of the cross-linked Halar compounds and the current commercial cryogenic seal materials, filled Teflon and Kel-F

  5. Quinoline: a promising antitubercular target.

    Science.gov (United States)

    Keri, Rangappa S; Patil, Siddappa A

    2014-10-01

    Tuberculosis (TB) remains a global public health problem in recent years. TB originated mainly from various strains of Mycobacterium tuberculosis, is a highly infectious and chronic disease with high infection rate since ancient times. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Among hetrocyclic compounds, quinoline compounds are important privileged structure in medicinal chemistry, are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain, quinoline-based compounds, also show effective anti-TB activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on this versatile core to provide an insight so that its full therapeutic potential can be utilized for the treatment tuberculosis. It is hoped that, this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic quinoline-based anti-TB drugs. PMID:25458785

  6. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  7. Anticorpos neutralizantes contra o vírus da Diarréia Viral Bovina (BVDV: comparação entre um imunógeno experimental atenuado e três vacinas comerciais inativadas Vaccination-induced neutralizing antibodies against bovine viral diarrhea virus (BVDV: comparison between an experimental modified-live vaccine and three comercial inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Marcelo de Lima

    2005-02-01

    Full Text Available Os títulos e duração de anticorpos neutralizantes contra o vírus da Diarréia Viral Bovina (BVDV induzidos por uma vacina experimental atenuada (vacina A: dose única foram comparados com os induzidos por três vacinas comerciais inativadas (B, C e D: duas doses com intervalo de 30 dias. Trinta dias após a vacinação (vacina A ou após a segunda dose (vacinas B, C e D, anticorpos neutralizantes contra o BVDV-1 foram detectados em todos os animais (12/12 do grupo A (título médio geométrico GMT=1612,7; em 32 de 36 animais do grupo B (GMT=14,3; 22 de 28 do grupo C (GMT=25,1; e em 16 de 30 do grupo D (GMT=40,0. Anticorpos frente ao BVDV-2 foram detectados em todos os animais do grupo A (GMT=151,0; em 27 de 36 do grupo B (GMT=10,0; 12 de 28 do grupo C (GMT=11,5 e em 10 de 30 animais do grupo D (GMT=10,0. No dia 180 após a vacinação, o número de animais que ainda apresentava anticorpos contra o BVDV-1 e os GMTs para cada grupo foram: vacina A (12/12, GMT=905,0; vacina B (30/36, GMT=28,3; vacina C (20/28, GMT=28,3; vacina D (14/30, GMT=16,1; e contra o BVDV-2 foram: vacina A (12/12, GMT=56,6; vacina B (18/36, GMT=16,8; vacina C (10/28, GMT=21,6 e vacina D (6/30, GMT=16,1. Os títulos médios (GMTs induzidos pela vacina A foram significativamente superiores aos demais, tanto para o BVDV-1 (PThe titers and duration of neutralizing antibodies against bovine viral diarrhea virus (BVDV induced by an experimental attenuated vaccine (vaccine A: one dose were compared to those induced by three commercial inactivated ones (B, C and D: two doses at a 30 day interval. Thirty days after vaccination (vaccine A or the second dose (vaccines B, C and D, neutralizing antibodies to BVDV-1 were detected in all calves (12/12 from group A (mean geometric titer GMT=1612.7; in 32 out of 36 from group B (GMT=14.3; 22/28 from group C (GMT=25.1; 16/30 from group D (GMT=40.0. Antibodies reacting with BVDV-2 were detected in all animals from group A (GMT=151.0; 27

  8. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

    Directory of Open Access Journals (Sweden)

    Alison E Mahan

    2016-03-01

    Full Text Available Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .

  9. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

    Science.gov (United States)

    Mahan, Alison E; Jennewein, Madeleine F; Suscovich, Todd; Dionne, Kendall; Tedesco, Jacquelynne; Chung, Amy W; Streeck, Hendrik; Pau, Maria; Schuitemaker, Hanneke; Francis, Don; Fast, Patricia; Laufer, Dagna; Walker, Bruce D; Baden, Lindsey; Barouch, Dan H; Alter, Galit

    2016-03-01

    Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  . PMID:26982805

  10. Role of antiviral antibodies in resistance against coxsackievirus B3 infection: interaction between preexisting antibodies and an interferon inducer.

    OpenAIRE

    Cho, C T; Feng, K. K.; McCarthy, V P; Lenahan, M F

    1982-01-01

    An experimental model of coxsackievirus B3 infection in newborn mice was utilized to examine the protective role of antiviral antibodies and an interferon inducer, polyinosinic acid-polycytidylic acid [poly(I:C)]. Subcutaneous administration to the infected mice of specific antiviral antibodies resulted in significant protection against coxsackievirus B3 infection. Antibody-treated animals had shortened viremia, early clearance of virus from tissues, and a reduced mortality rate. Dose respons...

  11. Adaptive responses to antibody based therapy.

    Science.gov (United States)

    Rodems, Tamara S; Iida, Mari; Brand, Toni M; Pearson, Hannah E; Orbuch, Rachel A; Flanigan, Bailey G; Wheeler, Deric L

    2016-02-01

    Receptor tyrosine kinases (RTKs) represent a large class of protein kinases that span the cellular membrane. There are 58 human RTKs identified which are grouped into 20 distinct families based upon their ligand binding, sequence homology and structure. They are controlled by ligand binding which activates intrinsic tyrosine-kinase activity. This activity leads to the phosphorylation of distinct tyrosines on the cytoplasmic tail, leading to the activation of cell signaling cascades. These signaling cascades ultimately regulate cellular proliferation, apoptosis, migration, survival and homeostasis of the cell. The vast majority of RTKs have been directly tied to the etiology and progression of cancer. Thus, using antibodies to target RTKs as a cancer therapeutic strategy has been intensely pursued. Although antibodies against the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have shown promise in the clinical arena, the development of both intrinsic and acquired resistance to antibody-based therapies is now well appreciated. In this review we provide an overview of the RTK family, the biology of EGFR and HER2, as well as an in-depth review of the adaptive responses undertaken by cells in response to antibody based therapies directed against these receptors. A greater understanding of these mechanisms and their relevance in human models will lead to molecular insights in overcoming and circumventing resistance to antibody based therapy. PMID:26808665

  12. Affinity purification of antibodies

    Science.gov (United States)

    Antibodies are provided in a variety of formats that includes antiserum, hybridoma culture supernatant or ascites. They can all be used successfully in crude form for the detection of target antigens by immunoassay. However, it is advantageous to use purified antibody in defined quantity to facil...

  13. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  14. Production Of Human Antibodies

    Science.gov (United States)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  15. RBC Antibody Screen

    Science.gov (United States)

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  16. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...

  17. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with 99mTc

    International Nuclear Information System (INIS)

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. 99mTc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with 99mTc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 μL MDP, 3.0 μg Sn2+, 1 mL of 99mTc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of 99mTc was about 2220 MBq (60 mCi). The evidences of the efficiency and quality of the methods here

  18. Bispecific antibodies and their use in applied research

    Directory of Open Access Journals (Sweden)

    Harshit Verma

    Full Text Available Bispecific antibodies (BsAb can, by virtue of combining two binding specificities, improve the selectivity and efficacy of antibody-based treatment of human disease. Antibodies with two distinct binding specificities have great potential for a wide range of clinical applications as targeting agents for in vitro and in vivo immunodiagnosis, therapy and for improving immunoassays. They have shown great promise for targeting cytotoxic effector cells, delivering radionuclides, toxins or cytotoxic drugs to specific targets, particularly tumour cells. The development of BsAb research goes through three main stages: chemical cross linking of murine-derived monoclonal antibody, hybrid hybridomas and engineered BsAb. This article is providing the potential applications of bispecific antibodies. [Vet World 2012; 5(12.000: 775-780

  19. Genetically delivered antibody protects against West Nile virus

    OpenAIRE

    Pereboev, Alexander; Borisevich, Viktoriya; Tsuladze, George; Shakhmatov, Mikhail; Hudman, Deborah; Kazachinskaia, Elena; Razumov, Ivan; Svyatchenko, Viktor; Loktev, Valery; Yamshchikov, Vladimir

    2007-01-01

    Gene-based delivery of recombinant antibody genes is a promising therapeutic strategy offering numerous advantages including sustained antibody levels, better safety profile and lower production cost. Here we describe generation of a recombinant antibody Fc-9E2 comprising a fusion protein between human Fc of IgG1 and a single-chain Fv derived from a hybridoma 9E2 secreting a mAb neutralizing West Nile virus (WNV). Fc-9E2 was shown to retain parental mAb's specificity and WNV-neutralizing capa...

  20. Current Status: Site-Specific Antibody Drug Conjugates.

    Science.gov (United States)

    Schumacher, Dominik; Hackenberger, Christian P R; Leonhardt, Heinrich; Helma, Jonas

    2016-05-01

    Antibody drug conjugates (ADCs), a promising class of cancer biopharmaceuticals, combine the specificity of therapeutic antibodies with the pharmacological potency of chemical, cytotoxic drugs. Ever since the first ADCs on the market, a plethora of novel ADC technologies has emerged, covering as diverse aspects as antibody engineering, chemical linker optimization and novel conjugation strategies, together aiming at constantly widening the therapeutic window for ADCs. This review primarily focuses on novel chemical and biotechnological strategies for the site-directed attachment of drugs that are currently validated for 2nd generation ADCs to promote conjugate homogeneity and overall stability. PMID:27003914

  1. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  2. Infección experimental con el virus de la diarrea viral bovina (VDVB genotipo 2 en terneros con anticuerpos neutralizantes al VDVB genotipo 1 Experimental infection with bovine viral diarrhea virus (BVDV genotype 2 in calves with neutralizing antibodies to BVDV genotype 1

    Directory of Open Access Journals (Sweden)

    J.I. Ronchi

    2001-01-01

    Full Text Available The aim of this study was to determine the consequences of the infection of BVDV genotype II (BVDV-2 in calves with preexisting immunity to BVDV-1 (induced by infection with wild type BVDV (Group A, 4 calves, or induced by vaccination with a killed BVDV-1 product (Group B, 2 calves. Group A and B were intranasally exposed to a field isolate of BVDV-2 (25ml x 10-7.8 TCID50/ml. Calves of Group A had erosions on the oral mucosa from 3 to 4 day post-challenge (DPC; moreover, intense salivation, mucous nasal secretion and sporadic diarrhea were observed from 4-14 DPC. Only one calf of Group B had diarrhea at 5 DPC. The average value of peripheral blood leukocytes (PBL previous to BVDV-2 challenge was 8,775 PBL/ml (±603 in calves of Group A and 9,975 PBL/ml (±1308 in calves of Group B. After BVDV-2 challenge there was leukopenia in Groups A and B. The minimal number of PBL of 5,875 PBL/ml (±311 was observed in Group A at 6 PDC (P <0.05. There were differences (P <0,05 in the average of PBL during the 17 DPC among challenged animals and uninfected controls. Moreover, a difference in the number of blood lymphocytes was observed at 6-7 DPC between virus exposed and control calves. BVDV was isolated from ocular swabs of 3 calves of Group A at 13 and 17 DPC and from PBL at 9 and 11 DPC. The neutralizing antibody titer (NT to both genotypes of BVDV was higher (P <0.05 in calves of Group A. Previous to virus challenge calves in this group had NT of 1:125 (geometric mean and 1:128 to BVDV-1 and -II, respectively. The NT rose to 1:2048 at 17 DPC to both Genotypes of BVDV. Calves in Group B had a NT of 1:16 to both BVDV-1 and -II previous to BVDV-2 challenge. At 17 DPC the NT rose to 1:64 and to 1:181 to BVDV-1 and -II, respectively. These results allow us to conclude that antibodies generated by natural infection or vaccination with BVDV-1 increased for BVDV-1 and -2 after the experimental challenge with BVDV-2.

  3. Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease

    Directory of Open Access Journals (Sweden)

    Bruno Mendes Roatt

    2014-06-01

    Full Text Available Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; and visceral leishmaniasis, which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. HIV infection, augments the severity of VL increasing the risk of developing active disease by 100 to 2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like Interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10 or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease.

  4. Antibody discovery: sourcing of monoclonal antibody variable domains.

    Science.gov (United States)

    Strohl, William R

    2014-03-01

    Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies (of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized. Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including various display technologies and amplification directly from B cells, are described. PMID:24168292

  5. Radiolabelled antibodies in imaging

    International Nuclear Information System (INIS)

    Recent technological advances make it possible to produce pure (monoclonal) antibodies in unlimited quantities without the need for continuous immunization of animals and to label these antibodies with a variety of radionuclides which can be traced by single-photon computed tomography. An outline review of the state of the art is presented, with particular reference to the imaging of myocardial infarcts and to tumour imaging studies using labelled monoclonal antibodies (sup(99m)Tc and 125I). Lengthy bibliography. (U.K.)

  6. [Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer].

    Science.gov (United States)

    Ozono, Seiichiro

    2014-09-01

    The effect of the anti-PD-1 antibody, nivolumab (ONO-4538/BMS-936558) on advanced renal cancer is promising. The present manuscript summarizes the use of this new drug in immunotherapy for renal cancer. PMID:25248891

  7. Immunotherapy of melanoma: present options and future promises.

    Science.gov (United States)

    Rotte, Anand; Bhandaru, Madhuri; Zhou, Youwen; McElwee, Kevin J

    2015-03-01

    Metastatic melanoma is notorious for its immune evasion and resistance to conventional chemotherapy. The recent success of ipilimumab, a human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in increasing the median survival time and stabilizing the disease progression renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment of patients with unresectable advanced melanoma, and pegylated interferon-α2b (p-IFN-α2b) is approved as an adjuvant for the treatment of patients with surgically resected high-risk melanoma. The present review describes the currently approved immune-modulators and the promising immune-based interventions that are currently in clinical trials. We present the four commonly used strategies to boost immune responses against the tumors; monoclonal antibodies, cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists of ongoing clinical trials include details of the trial phase, target patients, intervention details, status of the study, and expected date of completion. Further, our review discusses the challenges faced by immunotherapy and the various strategies adopted to overcome them. PMID:25589384

  8. Experimental study of application of anti-glomerular basement membrane antibodies neutralizing monoclonal antibody on anti-glomerular basement membrane nephritis rats%应用抗肾小球基底膜抗体的中和性单克隆抗体治疗抗肾小球基底膜肾炎大鼠的实验研究

    Institute of Scientific and Technical Information of China (English)

    肖静; 刘章锁; 聂志勇; 王雅楠; 赵国强

    2010-01-01

    目的 应用抗肾小球基底膜(GBM)抗体的中和性单克隆抗体注射抗GBM肾炎大鼠,观察各种生化指标及肾脏病理学的变化.方法 将Wistar大鼠随机分为5组,每组9只:(1)肾炎模型组:经尾静脉注入人抗GBM抗体;(2)正常对照Ⅰ组:经尾静脉注入非抗体性的健康人IgG;(3)对照Ⅱ组:经尾静脉注入抗GBM抗体的中和性单克降抗体;(4)干预Ⅰ组:经尾静脉注入人抗GBM抗体,第7天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体(1.5ml/100 g);(5)干预Ⅱ组:经尾静脉注入人抗GBM抗体,第14天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体.分别在实验后第7、14、21天观察大鼠24 h尿蛋白量、BUN、Scr和肾组织病理学的变化.结果 第21天干预Ⅰ组尿蛋白量为(16.62±5.53)g/d、BUN为(11.53±2.26)mmol/L、Scr为(102.46±16.86)μmol/L,均显著低于肾炎模型组(P<0.05);干预Ⅱ组较肾炎模型组也有所降低,但差异无统计学意义(P>0.05).干预Ⅰ组和干预Ⅱ组肾脏细胞增生、新月体的形成及免疫复合物的沉积均少于肾炎模型组,但干预Ⅰ组更为明显.对照Ⅰ组和对照Ⅱ组之间无明显变化.结论 早期应用抗GBM抗体的中和性单克隆抗体能够有效改善抗GBM肾炎大鼠的肾脏病变.%Objective To observe the effect of neutralizing monoclonal antibodies to antiglomerular basement membrane (GBM) antibody on anti-GBM nephritis rats. Methods Wistar rats were randomly divided into five groups: control group Ⅰ was a negative control and was injected with healthy human IgG via the caudal vein. Control group Ⅱ was injected with neutralizing monoclonal antibodies to anti-GBM antibody only. Anti- GBM nephritis group was injected with human anti-GBM antibody via the caudal vein only. Intervention group Ⅰ was injected with human anti-GBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 7. Intervention group Ⅱ was

  9. Anti-sulfotyrosine antibodies

    Science.gov (United States)

    Bertozzi, Carolyn R.; Kehoe, John; Bradbury, Andrew M.

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  10. HIV Antibody Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  11. Antinuclear antibody panel

    Science.gov (United States)

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...

  12. PRODUCTION OF MONOCLONAL ANTIBODIES

    Directory of Open Access Journals (Sweden)

    TOLKOVA E.S.

    2015-01-01

    Full Text Available The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  13. PRODUCTION OF MONOCLONAL ANTIBODIES

    OpenAIRE

    TOLKOVA E.S.

    2015-01-01

    The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  14. Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with an experimental recombinant HIV-1 IIIB gp160 vaccine. The National Institute of Allergy and Infectious Diseases-sponsored AIDS Vaccine Evaluation Group.

    OpenAIRE

    Lambert, J S; Viscidi, R; Walker, M. C.; Clayman, B; Winget, M; Wolff, M.; Schwartz, D H

    1997-01-01

    Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic volunteers with CD4 cell counts of >600 cells/mm3 who were enrolled in a phase I immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB-based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160-specific antibodies in parotid saliva, genital secretions, and serum. When the study was unblinded, it was determined that five volunteers had received rgp160 on a month 0, 1, 2, 3,...

  15. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  16. Human-like antibodies neutralizing Western equine encephalitis virus

    Science.gov (United States)

    Hülseweh, Birgit; Rülker, Torsten; Pelat, Thibaut; Langermann, Claudia; Frenzel, Andrè; Schirrmann, Thomas; Dübel, Stefan; Thullier, Philippe; Hust, Michael

    2014-01-01

    This study describes the development of the first neutralizing antibodies against Western equine encephalitis virus (WEEV), a member of the genus Alphavirus. WEEV is transmitted by mosquitoes and can spread to the human central nervous system, causing symptoms ranging from mild febrile reactions to life-threatening encephalitis. WEEV has been classified as a biological warfare agent by the US Centers for Disease Control and Prevention. No anti-WEEV drugs are currently commercially available. Neutralizing antibodies are useful for the pre- and post-exposure treatment of WEEV infections. In this study, two immune antibody gene libraries were constructed from two macaques immunized with inactivated WEEV. Four antibodies were selected from these libraries and recloned as scFv-Fc, with a human Fc part. These antibodies bound WEEV specifically in ELISA with little or no cross-reaction with other alphaviruses. They were further analyzed by immunohistochemistry. All binders were suitable for the intracellular detection of WEEV particles. Neutralizing activity was determined in vitro. Three of the four antibodies were found to be neutralizing; about 1 ng/mL of the best antibody (ToR69–3A2) neutralized 50% of 5x104 TCID50/mL. Due to its human-like nature with a germinality index of 89% (VH) and 91% (VL), the ToR69–3A2 antibody is a promising candidate for future passive vaccine development. PMID:24518197

  17. Development of Biodegradable Nanocarriers Loaded with a Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Andrew Gdowski

    2015-02-01

    Full Text Available Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid (PLGA nanoparticles using a water/oil/water double emulsion solvent evaporation technique. This method can be used to prepare protective polymeric nanoparticles for transporting functional antibodies to the cytoplasmic compartment of cancer cells. Nanoparticles were formulated and then characterized using a number of physical and biological parameters. The average nanoparticle size ranged from 221 to 252 nm with a low polydispersity index. Encapsulation efficiency of 16%–22% and antibody loading of 0.3%–1.12% were observed. The antibody molecules were released from the nanoparticles in a sustained manner and upon release maintained functionality. Our studies achieved successful formulation of antibody loaded polymeric nanoparticles, thus indicating that a PLGA-based antibody nanoformulation is a promising intracellular delivery vehicle for a large number of new intracellular antibody targets in cancer cells.

  18. Cell-Free Synthesis Meets Antibody Production: A Review

    Directory of Open Access Journals (Sweden)

    Marlitt Stech

    2015-01-01

    Full Text Available Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv and antigen binding fragments (Fab, have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufacture highly specific molecular recognition tools. However, as these technologies are accompanied by the drawbacks of being rather time-consuming and cost-intensive, efficient and powerful cell-free protein synthesis systems have been developed over the last decade as alternatives. So far, prokaryotic cell-free systems have been the focus of interest. Recently, eukaryotic in vitro translation systems have enriched the antibody production pipeline, as these systems are able to mimic the natural pathway of antibody synthesis in eukaryotic cells. This review aims to overview and summarize the advances made in the production of antibodies and antibody fragments in cell-free systems.

  19. Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    Full Text Available BACKGROUND: Botulinum neurotoxins (BoNT are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC, a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored. METHODS AND FINDINGS: We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A. The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro. CONCLUSIONS: An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components of an antibody antidote for BoNT exposure.

  20. Bacteriophages show promise as antimicrobial agents.

    Science.gov (United States)

    Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N

    1998-01-01

    The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed

  1. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  2. Production of monoclonal antibodies to Legionella pneumophila serogroups 1 and 6.

    OpenAIRE

    Para, M F; Plouffe, J F

    1983-01-01

    To better define the surface antigens of Legionella pneumophila for clinical and experimental purposes, we have produced monoclonal antibodies to L. pneumophila serogroups 1 and 6. Two hybridomas were produced in serogroup 1. One antibody, LP-I-17, recognized a serogroup-common antigen. The second antibody, LP-I-81, was specific for serogroup 1. This antibody was able to agglutinate bacterial cells belonging to the serogroup 1 reference strains. Philadelphia and Knoxville. Microagglutination ...

  3. Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

    Czech Academy of Sciences Publication Activity Database

    Bárta, P.; Lázníčková, A.; Lázníček, M.; Beckford, Denis R.; Beran, Miloš

    2013-01-01

    Roč. 56, č. 5 (2013), s. 280-288. ISSN 0362-4803 Grant ostatní: GA ČR(CZ) GAP304/10/1738 Institutional support: RVO:61389005 Keywords : radiopharmaceutical * 177Lu * 131I * nimotuzumab * EGFR * preclinical biodistribution Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.187, year: 2013

  4. The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice.

    Science.gov (United States)

    Krupka, Michal; Masek, Josef; Barkocziova, Lucia; Turanek Knotigova, Pavlina; Kulich, Pavel; Plockova, Jana; Lukac, Robert; Bartheldyova, Eliska; Koudelka, Stepan; Chaloupkova, Radka; Sebela, Marek; Zyka, Daniel; Droz, Ladislav; Effenberg, Roman; Ledvina, Miroslav; Miller, Andrew D; Turanek, Jaroslav; Raska, Milan

    2016-01-01

    Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag) OspC (rOspC) could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a) with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b) with free rOspC and Montanide PET GEL A; (c) with free rOspC and alum; or (d) with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants. PMID:26848589

  5. The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice.

    Directory of Open Access Journals (Sweden)

    Michal Krupka

    Full Text Available Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag OspC (rOspC could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b with free rOspC and Montanide PET GEL A; (c with free rOspC and alum; or (d with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.

  6. Beware of Products Promising Miracle Weight Loss

    Medline Plus

    Full Text Available ... Consumers Home For Consumers Consumer Updates Beware of Products Promising Miracle Weight Loss Share Tweet Linkedin Pin ... Office of Drug Evaluation. back to top Tainted Products For example, FDA has found weight-loss products ...

  7. Portable Zika Test Shows Promise in Monkeys

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_158704.html Portable Zika Test Shows Promise in Monkeys Easy-to-use ... News) -- A fast, inexpensive test that detects the Zika virus in monkeys might be useful for doctors ...

  8. Beware of Products Promising Miracle Weight Loss

    Medline Plus

    Full Text Available HHS U.S. Department of Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your ... Beware of Products Promising Miracle Weight Loss Share Tweet Linkedin Pin ...

  9. Portable Zika Test Shows Promise in Monkeys

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_158704.html Portable Zika Test Shows Promise in Monkeys Easy-to-use ... News) -- A fast, inexpensive test that detects the Zika virus in monkeys might be useful for doctors ...

  10. Big data in nephrology: promises and pitfalls.

    Science.gov (United States)

    Nadkarni, Girish N; Coca, Steven G; Wyatt, Christina M

    2016-08-01

    Data from the electronic health records hold great promise for nephrology research. However, due to significant limitations, reporting guidelines have been formulated for analyses conducted using electronic health records data. PMID:27418085

  11. On a road to promises that work

    OpenAIRE

    Cleary, Martin; Rooke, John; Koskela, Lauri

    2010-01-01

    This research into the applicability of ―Promise Based Management‖ in the UK construction sector examines the business side of construction as to where and how client and customer interact. A research opportunity to attend meetings and conduct interviews with clients and contractors on a major construction project in the North West of England gave first hand access to the various issues involved and enabled the researchers to draw some conclusions as to how promises are both a ...

  12. Less is sometimes more: promising practices reconsidered

    OpenAIRE

    Ferdinand, J; Simm, D.

    2006-01-01

    This paper focuses upon the notion of the 'promising practice' which has recently been advanced as a potential resolution to the problem of the perceived gap in UK competitiveness. The promising practices in which such great faith is being stored include those of: TQM, JIT, BPR, quality certification schemes and lean manufacturing. Whilst accepting the underlying principles, the need for organization to engage in the acquisition, absorption and exploitation of knowledge, we proceed to problem...

  13. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  14. Label-Free and Real-Time Detection of Antigen-Antibody Capture Processes Using the Oblique-Incidence Reflectivity Difference Technique

    International Nuclear Information System (INIS)

    We successfully label-free and real-time detect the capture processes of human immunoglobulin G (IgG)/goat anti-human IgG and mouse IgG/goat anti-mouse IgG antigen-antibody pairs with different concentrations using the oblique-incidence reflectivity difference (OIRD) method, and obtain the interaction kinetics curves and the interaction times. The experimental results prove that the OIRD method is a promising technique for label-free and real-time detection of the biomolecular interaction processes and achieving the quantitative information of interaction kinetics. (general)

  15. Label-Free and Real-Time Detection of Antigen-Antibody Capture Processes Using the Oblique-Incidence Reflectivity Difference Technique

    Science.gov (United States)

    He, Li-Ping; Dai, Jun; Sun, Yue; Wang, Jing-Yi; Lü, Hui-Bin; Wang, Shu-Fang; Jin, Kui-Juan; Zhou, Yue-Liang; Yang, Guo-Zhen

    2012-07-01

    We successfully label-free and real-time detect the capture processes of human immunoglobulin G (IgG)/goat anti-human IgG and mouse IgG/goat anti-mouse IgG antigen-antibody pairs with different concentrations using the oblique-incidence reflectivity difference (OIRD) method, and obtain the interaction kinetics curves and the interaction times. The experimental results prove that the OIRD method is a promising technique for label-free and real-time detection of the biomolecular interaction processes and achieving the quantitative information of interaction kinetics.

  16. Treating multiple sclerosis with monoclonal antibodies: a 2013 update.

    Science.gov (United States)

    Deiß, Annika; Brecht, Isabel; Haarmann, Axel; Buttmann, Mathias

    2013-03-01

    The third part of this in-depth review series on the treatment of multiple sclerosis (MS) with monoclonal antibodies covers the years 2010-2012. The natalizumab section gives a progressive multifocal leukoencephalopathy update, focusing on clinically relevant aspects. Furthermore, it outlines problems around natalizumab cessation and current evidence on therapeutic strategies thereafter. Finally, it reviews evidence on Janus-faced modes of natalizumab action besides anti-inflammatory effects, including proinflammatory effects. The section on alemtuzumab critically analyzes recent Phase III results and discusses which patients might be best suited for alemtuzumab treatment, and reviews the long-term immunological impact of this anti-CD52 antibody. The daclizumab section critically summarizes results from the Phase IIb SELECT/SELECTION trial and introduces the Phase III program. The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of these antibodies for MS therapy. Promising recent Phase II results on the anti-IL-17A antibody secukinumab (AIN457) are outlined and a short update on tabalumab (LY2127399) is given. Other highlighted antibodies currently being tested in MS patients include GNbAC1, BIIB033, MOR103 and MEDI-551. Finally, the authors give an update on the role monoclonal antibodies could play in the therapeutic armamentarium for MS in the medium term. PMID:23448220

  17. Targeting FcRn for the modulation of antibody dynamics.

    Science.gov (United States)

    Ward, E Sally; Devanaboyina, Siva Charan; Ober, Raimund J

    2015-10-01

    The MHC class I-related receptor, FcRn, is a multitasking protein that transports its IgG ligand within and across cells of diverse origins. The role of this receptor as a global regulator of IgG homeostasis and transport, combined with knowledge of the molecular details of FcRn-IgG interactions, has led to opportunities to modulate the in vivo dynamics of antibodies and their antigens through protein engineering. Consequently, the generation of half-life extended antibodies has shown a rapid expansion over the past decade. Further, FcRn itself can be targeted by inhibitors to induce decreased levels of circulating IgGs, which could have applications in multiple clinical settings. The engineering of antibody-antigen interactions to reduce antibody-mediated buffering of soluble ligand has also developed into an active area of investigation, leading to novel antibody platforms designed to result in more effective antigen clearance. Similarly, the target-mediated elimination of antibodies by internalizing, membrane bound antigens (receptors) can be decreased using novel engineering approaches. These strategies, combined with subcellular trafficking analyses of antibody/antigen/FcRn behavior in cells to predict in vivo behavior, have considerable promise for the production of next generation therapeutics and diagnostics. PMID:25766596

  18. Towards quantum-enhanced precision measurements: Promise and challenges

    Science.gov (United States)

    Zhang, Li-Jian; Xiao, Min

    2013-11-01

    Quantum metrology holds the promise of improving the measurement precision beyond the limit of classical approaches. To achieve such enhancement in performance requires the development of quantum estimation theories as well as novel experimental techniques. In this article, we provide a brief review of some recent results in the field of quantum metrology. We emphasize that the unambiguous demonstration of the quantum-enhanced precision needs a careful analysis of the resources involved. In particular, the implementation of quantum metrology in practice requires us to take into account the experimental imperfections included, for example, particle loss and dephasing noise. For a detailed introduction to the experimental demonstrations of quantum metrology, we refer the reader to another article ‘Quantum metrology’ in the same issue.

  19. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn; Sørensen, Per S

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  20. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  1. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  2. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? RBC Antibody Identification Share this page: Was this page helpful? Also known as: Alloantibody Identification; Antibody ID, RBC; RBC Ab ID Formal name: Red ...

  3. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  4. The Art of Making Antibodies.

    Science.gov (United States)

    Headon, Denis R.

    1986-01-01

    Provides background information for teachers on the nature and production of antibodies. Points out that the production of monoclonal antibodies blends the malignant with the beneficial to create a medical tool of exciting potential. (JN)

  5. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  6. Antibody-mediated neutralization of African swine fever virus: myths and facts.

    Science.gov (United States)

    Escribano, José M; Galindo, Inmaculada; Alonso, Covadonga

    2013-04-01

    Almost all viruses can be neutralized by antibodies. However, there is some controversy about antibody-mediated neutralization of African swine fever virus (ASFV) with sera from convalescent pigs and about the protective relevance of antibodies in experimentally vaccinated pigs. At present, there is no vaccine available for this highly lethal and economically relevant virus and all classical attempts to generate a vaccine have been unsuccessful. This failure has been attributed, in part, to what many authors describe as the absence of neutralizing antibodies. The findings of some studies clearly contradict the paradigm of the impossibility to neutralize ASFV by means of monoclonal or polyclonal antibodies. This review discusses scientific evidence of these types of antibodies in convalescent and experimentally immunized animals, the nature of their specificity, the neutralization-mediated mechanisms demonstrated, and the potential relevance of antibodies in protection. PMID:23159730

  7. Antibody Engineering and Therapeutics Conference

    OpenAIRE

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P; Weiner, Louis M.; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  8. Stem cell research and economic promises.

    Science.gov (United States)

    Caulfield, Timothy

    2010-01-01

    In the context of stem cell research, the promise of economic growth has become a common policy argument for adoption of permissive policies and increased government funding. However, declarations of economic and commercial benefit, which can be found in policy reports, the scientific literature, public funding policies, and the popular press, have arguably created a great deal of expectation. Can stem cell research deliver on the economic promise? And what are the implications of this economic ethos for the researchers who must work under its shadow? PMID:20579253

  9. Konjac glucomannan, a promising polysaccharide for OCDDS.

    Science.gov (United States)

    Zhang, Cui; Chen, Ji-da; Yang, Feng-Qing

    2014-04-15

    Oral colon targeting drug delivery system (OCDDS) is a highly effective formulation for drugs absorbed by colon, or to treat colonic diseases specifically. To obtain colon targeting, many pharmaceutical approaches have been studied, among which, taking advantage of specific degradation of excipients by colon enzymes is one of the most promising strategies. With properties of specific colon β-mannanase degradation, biocompatibility, gel-forming, low toxicity and high stability, konjac glucomannan (KGM) becomes a promising natural excipient for oral OCDDS. This paper summaries structure and properties of KGM, reviews achievements and prospects on KGM and modified konjac glucomannan about their application as pharmaceutic excipient for the OCDDS recently. PMID:24607175

  10. Radiolabeled antibodies as imaging agents

    International Nuclear Information System (INIS)

    The author gives a survey of the progress made on radioimmunodetection. Antibodies may now be more readily used in scintigraphy as a result of the development of labeling methods that apply more suitable radionuclides without significant loss of the antigen-binding activity. Antibodies to tumor-specific or tumor-associated antigens can now be produced in large quantities by monoclonal antibody technology

  11. A radioimmunoassay for determination of anti-actin antibodies

    International Nuclear Information System (INIS)

    The reaction of spontaneously occurring human anti-actin antibodies and experimentally produced rabbit anti-actin antibodies was investigated in a solid-phase radioimmunoassay (RIA). Three structurally different in vitro forms of actin, monomeric G-actin, filamentous F-actin and aggregated denatured actin were used as antigens. Human anti-actin antibodies reacted with F- and G-actin but not with aggregated actin, while rabbit anti-actin antibodies gave a strong reaction with all 3 forms of actin indicating differences in antibody specificities. The results of the anti-actin RIA were compared with those obtained by indirect immunofluorescence (IFL) on cryostat sections of rat stomach. The anti-actin RIA discriminated between patients' sera and control sera in most cases, although the indirect IFL test gave more conclusive results. The seemingly low sensitivity of the anti-actin RIA compared with that of indirect IFL test for detection of human anti-actin antibodies is probably due to favourable antigen distribution in tissue, not available in the solid phase. The anti-actin RIA was able to detect anti-actin antibodies in 8 out of 8 immunized rabbits although only two produced antibodies detectable by indirect IFL. The differences in reactivity between the two methods may depend on the presence of aggregated denatured actin in the antigen preparation used for immunization and exposure of the corresponding antigenic determinants of actin on the solid phase. (Auth.)

  12. Clinical Value of Tuberculosis Infection T Cell ELISPOT and TB Antibody Test in Experimental Tuberculosis of Bones and Joints%结核感染T细胞酶联免疫斑点试验与结核抗体试验在诊断骨关节结核中的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    钱晨

    2015-01-01

    -sons.The patients of T-SPOT.TB test group were tested by tuberculosis infection T cell enzyme-linked immunosorbent spot test,tuberculosis antibody test group were taken tuberculosis antibody test,comparative analysis of the sensitivity and speci-ficity of two diagnostic methods were contrastively analyzed.Results The sensitivity and specificity of T-SPOT.TB test group were 93.43% and 84.00%.The sensitivity and specificity of tuberculosis antibody in the experimental group were 40.44% and 53.85%.There was statistical difference between two groups (χ2 =184.62,7.86,all P <0.05).The false posi-tive rate and the false negative rate of T-SPOT.TB test group were 16.00% and 6.57%.The false positive rate and the false negative rate of tuberculosis antibodies in the experimental group were 26.92% and 59.56%,respectively.There was statis-tical difference between two groups (χ2 =7.86,156.18,all P <0.05).In addition,the positive and negative predictive values of T-SPOT.TB test group were 96.97% and 70.00%.Positive and negative predictive values of tuberculosis antibody in the experimental group were 88.71% and 14.74%.There was statistical difference between two groups (χ2 = 20.27,73.06,all P <0.01).Conclusion Compared to experimental tuberculosis antibody,TB infection of T cells ELISPOT test had high sen-sitivity and specificity in the diagnosis of bone and joint tuberculosis.It’s worthy of spreading.

  13. Monoclonal antibodies based on hybridoma technology.

    Science.gov (United States)

    Yagami, Hisanori; Kato, Hiroshi; Tsumoto, Kanta; Tomita, Masahiro

    2013-03-01

    Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs. PMID:24237029

  14. [Absorbable coronary stents. New promising technology].

    Science.gov (United States)

    Erbel, Raimund; Böse, Dirk; Haude, Michael; Kordish, Igor; Churzidze, Sofia; Malyar, Nasser; Konorza, Thomas; Sack, Stefan

    2007-06-01

    Coronary stent implantation started in Germany 20 years ago. In the beginning, the progress was very slow and accelerated 10 years later. Meanwhile, coronary stent implantation is a standard procedure in interventional cardiology. From the beginning of permanent stent implantation, research started to provide temporary stenting of coronary arteries, first with catheter-based systems, later with stent-alone technology. Stents were produced from polymers or metal. The first polymer stent implantation failed except the Igaki-Tamai stent in Japan. Newly developed absorbable polymer stents seem to be very promising, as intravascular ultrasound (IVUS) and optical coherence tomography have demonstrated. Temporary metal stents were developed based on iron and magnesium. Currently, the iron stent is tested in peripheral arteries. The absorbable magnesium stent (Biotronik, Berlin, Germany) was tested in peripheral arteries below the knee and meanwhile in the multicenter international PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) study. The first magnesium stent implantation was performed on July 30, 2004 after extended experimental testing in Essen. The magnesium stent behaved like a bare-metal stent with low recoil of 5-7%. The stent struts were absorbed when tested with IVUS. Stent struts were not visible by fluoroscopy or computed tomography (CT) as well as magnetic resonance imaging (MRI). That means, that the magnesium stent is invisible and therefore CT and MRI can be used for imaging of interventions. Only using micro-CT the stent struts were visible. The absorption process could be demonstrated in a patient 18 days after implantation due to suspected acute coronary syndrome, which was excluded. IVUS showed a nice open lumen. Stent struts were no longer visible, but replaced by tissue indicating the previous stent location. Coronary angiography after 4 months showed an ischemia-driven target lesion

  15. Capture technologies: Improvements and promising developments

    NARCIS (Netherlands)

    Blomen, E.; Hendriks, C.; Neele, F.

    2009-01-01

    In this status report we want to provide a comprehensive overview of the current status and promising technologies of CO2 capture by means of a literature review, in-house knowledge and interviews. We describe the technology, bottlenecks towards implementation and potential use. The results will be

  16. Beware of Products Promising Miracle Weight Loss

    Medline Plus

    Full Text Available ... For Consumers Consumer Updates Beware of Products Promising Miracle Weight Loss Share Tweet Linkedin Pin it More ... New Year’s resolution, know this: many so-called “miracle” weight loss supplements and foods (including teas and ...

  17. Beware of Products Promising Miracle Weight Loss

    Medline Plus

    Full Text Available ... En Español Search FDA Submit search Popular Content Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, ... Biologics Animal & Veterinary Cosmetics Tobacco Products For Consumers Home For Consumers Consumer Updates Beware of Products Promising ...

  18. Objectification Theory: Areas of Promise and Refinement

    Science.gov (United States)

    Moradi, Bonnie

    2011-01-01

    This article elaborates on three themes related to Szymanski, Moffitt, and Carr's major contribution aims. First, the article describes the promise of objectification theory as a grounding framework in research and practice, outlining how this theory integrates key aspects of several other important theoretical models. Second, this article…

  19. The promise of proteomics in animal science

    Science.gov (United States)

    Proteomics hold significant promise as a method for advancing animal science research. The use of this technology in animal science is still in its infancy. The ability of proteomics to simultaneously identify and quantify potentially thousands of proteins is unparalleled. In this review, we will...

  20. Responses to Broken Promises: Does Personality Matter?

    Science.gov (United States)

    Ho, Violet T.; Weingart, Laurie R.; Rousseau, Denise M.

    2004-01-01

    This paper examined the effects of personality traits on individuals' reactions to broken promises. We studied the effects of Neuroticism and Agreeableness on emotive and cognitive responses to breach and investigated whether these effects varied across different types (economic vs. social) and severity (high vs. low) of breach. We collected data…

  1. The Promises of Moral Foundations Theory

    Science.gov (United States)

    Musschenga, Bert

    2013-01-01

    In this article I examine whether Moral Foundations Theory can fulfil the promises that Haidt claims for the theory: that it will help in developing new approaches to moral education and to the moral conflicts that divide our diverse society. I argue that, first, the model that Haidt suggests for understanding the plurality of moralities--a shared…

  2. Beware of Products Promising Miracle Weight Loss

    Medline Plus

    Full Text Available ... Promising Miracle Weight Loss Share Tweet Linkedin Pin it More sharing options Linkedin Pin it Email Print Get Consumer Updates by E-mail ... removed from the market in October 2010 because it caused heart problems and strokes. “We’ve also ...

  3. Ideological Repositioning: Race, Social Justice, and Promise

    Science.gov (United States)

    Hodge, Samuel R.

    2014-01-01

    In this paper, I engage in discourse centrally located in the ideology of race in the United States of America juxtaposed to social justice with promise for tomorrow in higher education and beyond. I assert that social justice in kinesiology requires that once hired, retaining, securing tenured status, and promoting faculty of color means having…

  4. Recent progress of diagnostic and therapeutic approach to cancers using polyclonal or monoclonal antibodies

    International Nuclear Information System (INIS)

    Among the major topics of interest in cancer immunology, immunodiagnosis and immunotherapy with the antibodies are summarized historically and prospectively. The concept of injecting anti-tumor cell antibodies to localize tumors was first introduced in experimental systems by Pressman (1957). Since then, various trials have been achieved with human tumors using specific or nonspecific tumor-localizing antibodies diagnostically or therapeutically. In 1970's, successes in immunodiagnosis with the antibodies to oncofetal proteins also have been reported. Recently, there are numerous papers dealed with a series of external scanning or serotherapeutic trials by the use of monoclonal antibodies that bind selectively to tumor cells. Various relevant problems with them are discussed. (author)

  5. Monoclonal antibodies to Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Halpern, J L; Lundgren, B; Swan, J C; Parrillo, J E; Masur, H

    1989-01-01

    To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii...... reacted with human P. carinii, and none of four monoclonal antibodies to human P. carinii reacted with rat P. carinii. Two antibodies to human P. carinii reacted by immunofluorescence with only one human P. carinii isolate. Immunoblot studies identified major antigens of rat P. carinii with molecular...

  6. [Antibody therapy for Alzheimer's disease].

    Science.gov (United States)

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

  7. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2015-01-01

    and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps......Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...

  8. Monoclonal antibody as radiopharmaceutical

    International Nuclear Information System (INIS)

    The purification of anti-CEA monoclonal antibody 4C11 belonging to IgG sub(2a) subclass from mouse ascitis, donated by Ludwig Institute, Brazil was developed. The fragmentation of purified IgG sub(2a) by pepsin digestion and analytical studies by polyacrilamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) were done as preliminary assessment for their specific application in immunoscintigraphy. (author)

  9. Anticardiolipin antibodies in leptospirosis.

    OpenAIRE

    Rugman, F P; Pinn, G.; Palmer, M. F.; Waite, M.; Hay, C. R.

    1991-01-01

    The clinical course and serology of 16 cases of leptospirosis in an area with an unusually high endemic infection rate were studied to gain further insight into the pathology of the secondary immune phase that is typical of the disease. IgG anticardiolipin antibody concentrations were measured by immunoassay and found to be increased in eight serologically confirmed cases with severe complicated disease, compared with eight patients with relatively uncomplicated leptospirosis who had IgG anti...

  10. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  11. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  12. Antibody therapy for Ebola

    Science.gov (United States)

    Qiu, Xiangguo; Kobinger, Gary P

    2014-01-01

    Ebola viruses can cause severe hemorrhagic fever in humans and nonhuman primates with fatality rates up to 90%, and are identified as biosafety level 4 pathogens and CDC Category A Agents of Bioterrorism. To date, there are no approved therapies and vaccines available to treat these infections. Antibody therapy was estimated to be an effective and powerful treatment strategy against infectious pathogens in the late 19th, early 20th centuries but has fallen short to meet expectations to widely combat infectious diseases. Passive immunization for Ebola virus was successful in 2012, after over 15 years of failed attempts leading to skepticism that the approach would ever be of potential benefit. Currently, monoclonal antibody (mAbs)-based therapies are the most efficient at reversing the progression of a lethal Ebola virus infection in nonhuman primates, which recapitulate the human disease with the highest similarity. Novel combinations of mAbs can even fully cure lethally infected animals after clinical symptoms and circulating virus have been detected, days into the infection. These new developments have reopened the door for using antibody-based therapies for filovirus infections. Furthermore, they are reigniting hope that these strategies will contribute to better control the spread of other infectious agents and provide new tools against infectious diseases. PMID:24503566

  13. Vaccines for Healthcare-associated Infections: Promise and Challenge.

    Science.gov (United States)

    Knisely, Jane M; Liu, Baoying; Ranallo, Ryan T; Zou, Lanling

    2016-09-01

    As antibiotic resistance increases and the rate of antibiotic development slows, it is becoming more urgent to develop novel approaches to prevent and mitigate serious bacterial and fungal infections. Healthcare-associated infections (HAIs), including those caused by Clostridium difficile, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, carbapenem-resistant Enterobacteriaceae, and Candida species, are a major cause of morbidity, mortality, and healthcare costs. HAIs are also a key driver of antibiotic use. Vaccines directed toward these pathogens could help prevent a large number of HAIs and associated antibiotic use if administered to targeted populations. Despite numerous scientific and operational challenges, there are vaccine candidates in late-stage clinical development for C. difficile, S. aureus, and P. aeruginosa Basic, preclinical, and early clinical research to develop vaccines for other types of HAIs is also under way. In addition, other prophylactic immune interventions, such as monoclonal antibodies, for several of these pathogens are in advanced development. Here we describe the promise, challenges, and current pipeline of vaccines to prevent HAIs. PMID:27208045

  14. Potent Neutralization of Botulinum Neurotoxin/B by Synergistic Action of Antibodies Recognizing Protein and Ganglioside Receptor Binding Domain

    OpenAIRE

    Chen, Changchun; Wang, Shuhui; Wang, Huajing; Mao, Xiaoyan; Zhang, Tiancheng; Ji, Guanghui; Shi, Xin; Xia, Tian; Lu, Weijia; Zhang, Dapeng; Dai, Jianxin; Guo, Yajun

    2012-01-01

    Background Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed. Methods and Findings We selected 3 neutrali...

  15. Epigenetic Epidemiology: Promises for Public Health Research

    OpenAIRE

    Bakulski, Kelly M.; Fallin, M. Daniele

    2014-01-01

    Epigenetic changes underlie developmental and age related biology. Promising epidemiologic research implicates epigenetics in disease risk and progression, and suggests epigenetic status depends on environmental risks as well as genetic predisposition. Epigenetics may represent a mechanistic link between environmental exposures, or genetics, and many common diseases, or may simply provide a quantitative biomarker for exposure or disease for areas of epidemiology currently lacking such measure...

  16. Promising Products for Printing and Publishing Market

    Directory of Open Access Journals (Sweden)

    Renata Činčikaitė

    2011-04-01

    Full Text Available The article surveys printing and publishing market and its strong and weak aspects. The concept of a new product is described as well as its lifetime and the necessity of its introduction to the market. The enterprise X operating on the market is analyzed, its strong and weak characteristics are presented. The segmentation of the company consumers is performed. On the basis of the performed analysis the potential promising company products are defined.Article in Lithuanian

  17. ABOUT NEW PROMISING MATHEMATICAL TOOLS OF CONTROLLING

    OpenAIRE

    Orlov A. I.

    2015-01-01

    Based on an objective analysis, it must be noted that in the arsenal of managers, especially foreign ones, there is practically no fundamentally new methods and tools. However, promising mathematical and instrumental methods of controlling actively developed in our country. In the XXI century it developed a new paradigm of mathematical methods of economics and produced more than 10 books, developed in accordance with this paradigm. The new paradigm is based on the modern development of mathem...

  18. PROMISING STRATEGIES FOR THE PREVENTION OF DEMENTIA

    OpenAIRE

    Middleton, Laura; Yaffe, Kristine

    2009-01-01

    The incidence and prevalence of dementia is expected to increase several fold in the coming decades. Given that the current pharmaceutical treatment of dementia can only modestly improve symptoms, risk factor modification remains the cornerstone for dementia prevention. Some of the most promising strategies for the prevention of dementia include vascular risk factor control, cognitive activity, physical activity, social engagement, diet, and recognition of depression. In observational studies...

  19. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    Science.gov (United States)

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors. PMID:27133571

  20. A Simple Methodology for Conversion of Mouse Monoclonal Antibody to Human-Mouse Chimeric Form

    Directory of Open Access Journals (Sweden)

    Vinh T. Dang

    2013-01-01

    Full Text Available Passive immunotherapy has mainly been used as a therapy against cancer and inflammatory conditions. Recent studies have shown that monoclonal antibody-(mAb- based passive immunotherapy is a promising approach to combat virus infection. Specific mouse mAbs can be routinely generated in large amounts with the use of hybridoma technology but these cannot be used for therapy in human beings due to their immunogenicity. Therefore, the development of chimeric and humanized mAbs is important for therapeutic purpose. This is facilitated by a variety of molecular techniques like recombinant DNA technology and the better understanding of the structure and function of antibody. The human-mouse chimeric forms allow detailed analysis of the mechanism of inhibition and the potential for therapeutic applications. Here, a step-by-step description of the conversion process will be described. The commercial availability of the reagents required in each step means that this experimentation can be easily set up in research laboratories.

  1. Therapeutic application of monoclonal antibodies in multiple sclerosis: focus on alemtuzumab

    Directory of Open Access Journals (Sweden)

    Niino M

    2011-10-01

    Full Text Available Masaaki NiinoDepartment of Clinical Research, Hokkaido Medical Center, Sapporo, JapanAbstract: Recent progress in the treatment of multiple sclerosis (MS is significant, and the potential of monoclonal antibodies (mAbs for the treatment of MS has been highlighted. Natalizumab demonstrated a high level of efficacy for MS and is the first mAb to be approved for treatment of MS. Clinical trials of several types of mAbs for treatment of MS are in progress, and mAbs are expected to become the new choice of treatment for MS. Alemtuzumab is one of the most promising mAbs for treatment for MS, despite some side effects to be considered such as autoimmune hyperthyroidism, Goodpasture’s syndrome, and autoimmune idiopathic thrombocytopenic purpura. Any therapeutic agents for MS may carry risks of short- or long-term side effects; however, information regarding the long-term side effects of these new agents is lacking. Long-term adverse effects can often be recognized after the approval of agents. Here, recent progress on mAbs for the treatment of MS is reviewed, with a focus on alemtuzumab.Keywords: multiple sclerosis, monoclonal antibody, alemtuzumab, therapy, experimental autoimmune encephalomyelitis

  2. Second antibody clearance of radiolabeled antibody in cancer radioimmunodetection.

    OpenAIRE

    Sharkey, R M; Primus, F J; Goldenberg, D. M.

    1984-01-01

    The imaging of tumors using radiolabeled antibodies previously has required the implementation of computer-assisted subtraction techniques to reduce background radioactivity. A decrease in radioactivity in the blood of hamsters bearing human colonic tumor xenografts has been achieved by administering a second antibody directed against a radiolabeled primary antibody to carcinoembryonic antigen (CEA). This method was found to reduce the level of blood radioactivity by a factor of 4 within 2 hr...

  3. Antibody-protein A conjugated quantum dots for multiplexed imaging of surface receptors in living cells.

    Science.gov (United States)

    Jin, Takashi; Tiwari, Dhermendra K; Tanaka, Shin-Ichi; Inouye, Yasushi; Yoshizawa, Keiko; Watanabe, Tomonobu M

    2010-11-01

    To use quantum dots (QDs) as fluorescent probes for receptor imaging, QD surface should be modified with biomolecules such as antibodies, peptides, carbohydrates, and small-molecule ligands for receptors. Among these QDs, antibody conjugated QDs are the most promising fluorescent probes. There are many kinds of coupling reactions that can be used for preparing antibody conjugated QDs. Most of the antibody coupling reactions, however, are non-selective and time-consuming. In this paper, we report a facile method for preparing antibody conjugated QDs for surface receptor imaging. We used ProteinA as an adaptor protein for binding of antibody to QDs. By using ProteinA conjugated QDs, various types of antibodies are easily attached to the surface of the QDs via non-covalent binding between the F(c) (fragment crystallization) region of antibody and ProteinA. To show the utility of ProteinA conjugated QDs, HER2 (anti-human epidermal growth factor receptor 2) in KPL-4 human breast cancer cells were stained by using anti-HER2 antibody conjugated ProteinA-QDs. In addition, multiplexed imaging of HER2 and CXCR4 (chemokine receptor) in the KPL-4 cells was performed. The result showed that CXCR4 receptors coexist with HER2 receptors in the membrane surface of KPL-4 cells. ProteinA mediated antibody conjugation to QDs is very useful to prepare fluorescent probes for multiplexed imaging of surface receptors in living cells. PMID:20835432

  4. Promises, Promises, and Not a Job in Sight; Broke Ass State; The Violinist

    OpenAIRE

    Callahan, Lauren

    2011-01-01

    Promises, Promises, and Not a Job in Sight Abstract: This piece was produced in October 2010 and looked at California’s impending gubernatorial race. Jobs and the economy were a big issue in that campaign between Meg Whitman and Jerry Brown, and I set out to answer whether either candidate could provide the economic relief they were promising. Resources: Mathews, Joe and Mark Paul. California Crackup: How Reform Broke the Golden State and How We Can Fix It. 2010, University of California Pre...

  5. RNAi-based validation of antibodies for reverse phase protein arrays

    Directory of Open Access Journals (Sweden)

    Sahin Özgür

    2010-12-01

    Full Text Available Abstract Background Reverse phase protein arrays (RPPA have been demonstrated to be a useful experimental platform for quantitative protein profiling in a high-throughput format. Target protein detection relies on the readout obtained from a single detection antibody. For this reason, antibody specificity is a key factor for RPPA. RNAi allows the specific knockdown of a target protein in complex samples and was therefore examined for its utility to assess antibody performance for RPPA applications. Results To proof the feasibility of our strategy, two different anti-EGFR antibodies were compared by RPPA. Both detected the knockdown of EGFR but at a different rate. Western blot data were used to identify the most reliable antibody. The RNAi approach was also used to characterize commercial anti-STAT3 antibodies. Out of ten tested anti-STAT3 antibodies, four antibodies detected the STAT3-knockdown at 80-85%, and the most sensitive anti-STAT3 antibody was identified by comparing detection limits. Thus, the use of RNAi for RPPA antibody validation was demonstrated to be a stringent approach to identify highly specific and highly sensitive antibodies. Furthermore, the RNAi/RPPA strategy is also useful for the validation of isoform-specific antibodies as shown for the identification of AKT1/AKT2 and CCND1/CCND3-specific antibodies. Conclusions RNAi is a valuable tool for the identification of very specific and highly sensitive antibodies, and is therefore especially useful for the validation of RPPA-suitable detection antibodies. On the other hand, when a set of well-characterized RPPA-antibodies is available, large-scale RNAi experiments analyzed by RPPA might deliver useful information for network reconstruction.

  6. Antibody Glossary —

    Science.gov (United States)

    The components of the immune system have diverse roles in the initial development of cancers, progression of early-stage malignancies to invasive tumors, establishment of metastatic lesions, tumor dormancy, and response or resistance to therapy. Characterizing the components of the immune system and their functional status in tissues and in tumors requires the use of highly specific reagents. Researchers employ antibodies in a variety of in vitro and in vivo applications to delineate, enrich, or deplete specific immune subsets in order to understand their role(s) in tumorigenesis. This is a glossary of validated reagents and protocols that are useful for functional phenotyping of the immune system in murine cancer models.

  7. VIRAL ANTIBODIES IN PRESCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    S. Saidi

    1974-08-01

    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  8. Radioimmunoassay for antigliadin-antibodies using 14C-labelled gliadin

    International Nuclear Information System (INIS)

    A sensitive radioimmunoassay for antibodies to gliadin has been developed. Gliadin from wheat gluten was labelled with [1-14C]acetic anhydride to a specific activity of 2.6 x 106 dpm/mg. Immunological evidence is presented that the antigen was not essentially altered by the labelling procedure. Experimentally-induced antigliadin antibodies or sera of patients with coeliac disease (CD) were reacted with labelled gliadin and the immune complexes formed precipitated by antiglobulin. Precipitating antibodies were determined by incubating CD sera with labelled gliadin and measuring the radioacticity in precipitates formed without the addition of second antibody. Comparison with other methods for the detection of antigliadin antibodies, including immunoelectrophoresis, immunodiffusion and passive hemagglutination indicated that total and precipitating antibodies were determined only by RIA. The assay also provides information on the immunoglobulin class of antigliadin-antibodies present in sera of patients with coeliac disease

  9. Ruthenium Sesquisilicide: A Promising Thermoelectric Material

    Science.gov (United States)

    Vining, Cronin B.

    1993-01-01

    Report describes experimental investigation of thermoelectric properties of ruthenium sesquisilicide (RU2Si3). Suggests suitably doped Ru2Si3 could have thermoelectric figures of merit two or more times as large as SiGe.

  10. Antibodies to watch in 2015

    OpenAIRE

    Reichert, Janice M

    2014-01-01

    The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 6 antibody therapeutics (sec...

  11. Metrics for antibody therapeutics development

    OpenAIRE

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  12. Empowered Antibody Therapies - IBC conference.

    Science.gov (United States)

    Herold, Jens

    2010-10-01

    The Empowered Antibody Therapies conference, held in Burlingame, CA, USA, included topics covering new therapeutic developments in the field of multispecific antibodies. This conference report highlights selected presentations on DVD-Igs from Abbott Laboratories, ImmTACs from Immunocore, 'Dock-and-Lock' technology from Immunomedics, the bispecific BiTE antibody blinatumomab from Micromet, and Triomabs from TRION Pharma and Fresenius Biotech. PMID:20878591

  13. Wave modelling in the PROMISE project

    OpenAIRE

    Monbaliu, J.; Hargreaves, J. C.; Carretero, J.-C.; Gerritsen, H.; Flather, R.

    1999-01-01

    The primary objective of the EC-MAST III project PROMISE (Pre-Operational Modelling In the Seas of Europe) is to develop a framework to optimize the application of existing pre-operational dynamical models of the North Sea in order to quantify the rates and scales of the exchange of sediments between the coast and the near-shore zone. This framework should also be applicable to other coastal areas and for broader management applications. One of the components of this framework is the developm...

  14. MEMORY AND PROMISE IN ARENDT AND NIETZSCHE

    Directory of Open Access Journals (Sweden)

    VANESSA LEMM

    2006-01-01

    Full Text Available This article investigates and compares the value and significance that Arendt and Nietzsche attribute to the role played by memory and by the promise in constituting the political and in safeguarding the freedom and plurality of human actionEste artículo compara el valor y el significado que Arendt y Nietzsche otorgan a la memoria y a la promesa para la constitución de lo político así como para la salvaguardia de la libertad y de la pluralidad humana

  15. Small fusion reactors: problems, promise, and pathways

    International Nuclear Information System (INIS)

    The prevalent vision of magnetic fusion as a central-station power plant projects a high-technology, low-power-density nuclear boiler that may require high energy costs to be economic. Smaller, higher-power-density approaches can reduce the impact of the fusion power core and associated support equipment on the overall cost equation for fusion. In the course of attaining sizes, power capacity, and costs that are more in line with alternative energy sources, a range of problems, promise, and pathways can be identified. The issues related to these more compact systems are addressed on the basis of generic reactor models

  16. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... (iii) antibody numbering and IMGT. Here, we review “antibody informatics,” which may integrate the above three fields so that bridging the gaps between industrial needs and academic solutions can be accelerated. This article is part of a Special Issue entitled: Recent advances in molecular engineering...

  17. Tumor imaging with monoclonal antibodies

    International Nuclear Information System (INIS)

    Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab)2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

  18. Measuring the sequence-affinity landscape of antibodies with massively parallel titration curves

    OpenAIRE

    Adams, Rhys M.; Kinney, Justin B.; Mora, Thierry; Walczak, Aleksandra M.

    2016-01-01

    Despite the central role that antibodies play in the adaptive immune system and in biotechnology, much remains unknown about the quantitative relationship between an antibody's amino acid sequence and its antigen binding affinity. Here we describe a new experimental approach, called Tite-Seq, that is capable of measuring binding titration curves and corresponding affinities for thousands of variant antibodies in parallel. The measurement of titration curves eliminates the confounding effects ...

  19. Promises in intelligent plant control systems

    International Nuclear Information System (INIS)

    The control system is the brain of a power plant. The traditional goal of control systems has been productivity. However, in nuclear power plants the potential for disaster requires safety to be the dominant concern, and the worldwide political climate demands trustworthiness for nuclear power plants. To keep nuclear generation as a viable option for power in the future, trust is the essential critical goal which encompasses all others. In most of today's nuclear plants the control system is a hybrid of analog, digital, and human components that focuses on productivity and operates under the protective umbrella of an independent engineered safety system. Operation of the plant is complex, and frequent challenges to the safety system occur which impact on their trustworthiness. Advances in nuclear reactor design, computer sciences, and control theory, and in related technological areas such as electronics and communications as well as in data storage, retrieval, display, and analysis have opened a promise for control systems with more acceptable human brain-like capabilities to pursue the required goals. This paper elaborates on the promise of futuristic nuclear power plants with intelligent control systems and addresses design requirements and implementation approaches

  20. Creating Ordered Antibody Arrays with Antibody-Polymer Conjugates

    Science.gov (United States)

    Dong, Xuehui; Obermeyer, Allie; Olsen, Bradley

    Antibodies are a category of functional proteins that play crucial roles in the immune system and have been widely applied in the area of cancer therapeutics, targeting delivery, signal detection, and sensors. Due to the extremely large size and lack of specific functional groups on the surface, it is challenging to functionalize antibodies and manipulate the ordered packing of antibodies in an array with high density and proper orientation, which is critical to achieve outstanding performance in materials. In this work, we demonstrate an efficient and facile approach for preparing antibody-polymer conjugates with two-step sequential ``click'' reaction to form antibody-polymer block copolymers. Highly ordered nanostructures are fabricated based on the principles of block copolymer self-assembly. The nanostructures are studied with both small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Lamellae with alternating antibody domain and polymer domain are observed with an overall domain size of ~50 nm. The nanostructure not only increases the packing density and promotes proper orientation of the antibody, but also provides possible channel to facilitate substrate transportation and improves the stability of the antibody.

  1. Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

    DEFF Research Database (Denmark)

    Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S;

    2009-01-01

    Summary Graves' disease is characterized by production of agonist antibodies to the thyroid-stimulating hormone receptor (TSHR), but knowledge of the genetic and somatic events leading to their aberrant production is limited. We describe the genetic analysis of two monoclonal antibodies (mAbs) with......-determining regions (CDRs) and the framework regions. The cloned IGHV and IGLV genes were confirmed to have TSAb properties in experiments in which they were expressed as recombinant Fabs (rFabs). In other experiments, we swapped the IGLV genes with IGHV genes by constructing chimeric rFabs and showed that the...... experimentally immunized mice, multiple pathogenic antibodies to TSHR can arise from a single clone by a series of somatic mutations in the V-region genes and may give an insight into how such antibodies develop spontaneously in autoimmune Graves' disease....

  2. Lepromatous leprosy patients produce antibodies that recognise non-bilayer lipid arrangements containing mycolic acids

    Directory of Open Access Journals (Sweden)

    Isabel Baeza

    2012-12-01

    Full Text Available Non-bilayer phospholipid arrangements are three-dimensional structures that form when anionic phospholipids with an intermediate structure of the tubular hexagonal phase II are present in a bilayer of lipids. Antibodies that recognise these arrangements have been described in patients with antiphospholipid syndrome and/or systemic lupus erythematosus and in those with preeclampsia; these antibodies have also been documented in an experimental murine model of lupus, in which they are associated with immunopathology. Here, we demonstrate the presence of antibodies against non-bilayer phospholipid arrangements containing mycolic acids in the sera of lepromatous leprosy (LL patients, but not those of healthy volunteers. The presence of antibodies that recognise these non-bilayer lipid arrangements may contribute to the hypergammaglobulinaemia observed in LL patients. We also found IgM and IgG anti-cardiolipin antibodies in 77% of the patients. This positive correlation between the anti-mycolic-non-bilayer arrangements and anti-cardiolipin antibodies suggests that both types of antibodies are produced by a common mechanism, as was demonstrated in the experimental murine model of lupus, in which there was a correlation between the anti-non-bilayer phospholipid arrangements and anti-cardiolipin antibodies. Antibodies to non-bilayer lipid arrangements may represent a previously unrecognised pathogenic mechanism in LL and the detection of these antibodies may be a tool for the early diagnosis of LL patients.

  3. Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

    OpenAIRE

    Rieder, Florian; Lopez, Rocio; Franke, Andre; Wolf, Alexandra; Schleder, Stephan; Dirmeier, Andrea; Schirbel, Anja; Rosenstiel, Philip; Dotan, Nir; Schreiber, Stefan; Rogler, Gerhard; Klebl, Frank

    2011-01-01

    Introduction Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. Methods 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L)...

  4. Antiphospholipid antibodies and infertility.

    Science.gov (United States)

    Chighizola, C B; de Jesus, G R

    2014-10-01

    Since the late 1980s some publications have proposed that antiphospholipid antibodies (aPL) may have some relationship with infertility, considering reported deleterious effects that aPL exert on trophoblast proliferation and growth. Although not included in current classification criteria for antiphospholipid syndrome, many physicians investigate for aPL in patients with a history of infertility, including antibodies not listed in classification criteria, and most of those patients will receive anticoagulant therapy if any of those antibodies have a result considered positive. A review of literature was conducted searching for studies that investigated the association of aPL and infertility and if aPL positivity alters in vitro fertilization (IVF) outcome. The definition of infertility, routine work-up to exclude other causes of infertility, definition of IVF failure as inclusion criteria and control populations were heterogeneous among studies. Most of them enrolled women over 40 years of age, and exclusion of other confounding factors was also inconsistent. Of 29 studies that assessed aPL positivity rates in infertile women, the majority had small sample sizes, implying a lack of power, and 13 (44.8%) reported higher frequency of aPL in infertile patients compared to controls, but most of them investigated a panel of non-criteria aPL tests, whose clinical significance is highly controversial. Only two studies investigated all three criteria tests, and medium-high titer of anticardiolipin cut-off conforming to international guidelines was used in one study. Considering IVF outcome, there was also disparity in this definition: few studies assessed the live birth rate, others the implantation rate. Of 14 publications that addressed the relationship between aPL and IVF outcome, only two described a detrimental effect of these autoantibodies. In conclusion, available data do not support an association between aPL and infertility, and aPL positivity does not seem to

  5. Enhanced antigen detection in immunohistochemical staining using a 'digitized' chimeric antibody.

    Science.gov (United States)

    Eng, Hui-Yan; Wang, Cheng-I; Xue, Yuezhen; Lee, Chia-Yin; Zulkifli, Sarah Binte; Chiam, Poh-Cheang; Ghadessy, Farid J; Lane, David P

    2016-01-01

    The immunohistochemical (IHC) staining of mouse tissue sections using antibodies of mouse origin can result in high nonspecific background due to the staining of endogenous immunoglobulins (Igs) by enzyme-conjugated secondary antibodies. In order to obviate this issue, we developed a chimeric mouse-human anti-p53 monoclonal antibody (MH242) by grafting the variable regions of a known mouse antibody into a human Ig scaffold. This facilitated use of an anti-human secondary antibody, and resulted in near-zero background when compared with its parental mouse monoclonal antibody (PAb242). Furthermore, the chimeric antibody enabled reproducible detection of mutant p53 (homozygous R172H) expression in mouse tissue, an observation hitherto largely equivocal based on the use of existing antibodies. The approach we describe leads to the generation of tractable antibody reagents, whose integrity can be readily verified through DNA sequencing of expressor plasmids. The wide-spread adoption of such 'digitized' antibodies should reduce experimental disparities that can commonly arise through variations in antibody quality. PMID:26508747

  6. Detection of anti-Toxoplasma gondii antibodies in experimentally and naturally infected non-human primates by Indirect Fluorescence Assay (IFA and indirect ELISA Detecção de anticorpos anti-Toxoplasma gondii por meio das técnicas de Imunofluorescência Indireta e ELISA Indireto em primatas experimentalmente e naturalmente infectados

    Directory of Open Access Journals (Sweden)

    Andréa Bouer

    2010-03-01

    Full Text Available The Indirect Fluorescence Assay (IFA and the indirect ELISA were comparatively used to detect IgG and IgM antibodies for Toxoplasma gondii in experimentally and naturally infected primates. In the experimentally infected group, antibodies of diagnostic value were detected at day 9 post-infection (PI with the IFA (IgG and IgM and with IgG-ELISA. IgM-ELISA detected antibodies for T. gondii starting at day 3 PI until the end of the experiment (102 days PI. Of the 209 naturally infected sera tested, from many zoos of State of Sao Paulo, 64.59 and 67.94% were positive in the IgG-IFA test and IgG-ELISA respectively. IgM-ELISA test detected seropositivity in 52.63% of the sera although IgM-IFA test detected it in only in 0.96% of the samples. The differential toxoplasmosis diagnosis was accomplished with Neospora caninum by IFA, observing 61 (29.2% seropositive animals for this parasite and 149 (70.8% negative. Sixty animals were positive for both T. gondii and N. caninum. Pneumonia, splenomegaly, and intestinal ulcers were macroscopically observed. Unremarkable interstitial pneumonia, enteritis, colitis, splenitis, and glomerulitis were microscopically observed. The immunohistochemical stain could not detect the presence of T. gondii in the tissues of the animals infected experimentally.Detectou-se anticorpos das classes IgG e IgM anti-Toxoplasma gondii em primatas experimentalmente e naturalmente infectados, utilizando-se como técnicas comparativas a RIFI e o ELISA-teste. No grupo dos primatas experimentalmente infectados, anticorpos de valor diagnóstico foram detectados a partir do 9º dia de infecção tanto na RIFI (IgG e IgM como no ELISA-IgG. O ELISA IgM detectou anticorpos a partir do 3º dia de infecção até o final do experimento (102 dias pós-infecção. Dos 209 soros dos primatas naturalmente infectados, de diversos zoológicos do Estado de São Paulo, 64,59 e 67,94% mostraram-se positivos na RIFI-IgG e no ELISA-IgG, respectivamente. O

  7. Prenatal pharmacogenomics: a promising area for research.

    Science.gov (United States)

    Dorfman, E H; Cheng, E Y; Hebert, M F; Thummel, K E; Burke, W

    2016-08-01

    Clinical applications of prenatal genetic screening currently focus on detection of aneuploidy and other genetic diseases in the developing fetus. Growing evidence suggests that the fetal genome may also be informative about fetal exposures through contributions to placental transport as well as placental and fetal metabolism. Possible clinical applications of prenatal pharmacogenomic screening include prospective optimization of medication selection and dosage, as well as retrospective assessment of whether a fetus was previously exposed to significant risk. Newly available noninvasive methods of prenatal genetic screening mean that relevant fetal genotypes could be made available to obstetricians for use in management of a current pregnancy. This promising area for research merits more attention than it has thus far received.The Pharmacogenomics Journal advance online publication, 10 May 2016; doi:10.1038/tpj.2016.33. PMID:27168097

  8. Underexploited tropical plants with promising economic value

    Energy Technology Data Exchange (ETDEWEB)

    1975-01-01

    The apparent advantages of staple plants over the minor tropical plants often result only from the disproportionate research attention they have been given. A world-wide inquiry resulted in a list of 400 promising but neglected species. The 36 most important species are described in compact monographs and concern cereals (Echinochloa turnerana, grain amaranths, quinua and Zosterea mazina), roots and tubers (Arrachacha, cocoyams and taro), vegetables (chaya, hearts of palms, wax gourd, winged bean), fruits (durian, mangosteen, naranjilla, pejibaye, pummelo, soursop, uvilla), oilseeds (babassu palm, buffalo gourd, Caryocar species, Hessenia polycarpa and jojoba), forage (Acacia albida, Brosimum alicastrum Cassia sturtii, saltbushes and tamarugo) and other crops (buriti palm, Calathea lutea, candelilla, guar, guayule, Paspalum vaginatum, ramie and Spirulina).

  9. GOLD NANOPARTICLES: PROMISING AND POTENTIAL NANOMATERIAL

    Directory of Open Access Journals (Sweden)

    Madhuri Shringirishi*, S.K. Prajapati , Alok Mahor , Shashi Alok , Poonam Yadav and Amita Verma

    2013-11-01

    Full Text Available Gold nanoparticles (AuNPs have appeared as an attractive candidate for delivery of various drug molecules or considered as extraordinary molecular carriers for the targeting, intracellular trafficking and delivery of a huge array of biomolecules including DNA, RNA, proteins, peptides, drugs, genes and other molecules of therapeutic significance. Particularly gold nanoparticles have attracted intensive interest, because they are easily prepared, have low toxicity and can be readily attached to molecules of biological interest. More and more research shows that AuNPs-based technologies are becoming promising approaches in drug and gene delivery, liver targeting, brain targeting, cancer research and AIDS treatment. The present review focuses on synthesis and functionalization methods of GNPs, the past researchs and reviews about GNPs, their emerging applications and uses and their future prospects.

  10. The promise of Lean in health care.

    Science.gov (United States)

    Toussaint, John S; Berry, Leonard L

    2013-01-01

    An urgent need in American health care is improving quality and efficiency while controlling costs. One promising management approach implemented by some leading health care institutions is Lean, a quality improvement philosophy and set of principles originated by the Toyota Motor Company. Health care cases reveal that Lean is as applicable in complex knowledge work as it is in assembly-line manufacturing. When well executed, Lean transforms how an organization works and creates an insatiable quest for improvement. In this article, we define Lean and present 6 principles that constitute the essential dynamic of Lean management: attitude of continuous improvement, value creation, unity of purpose, respect for front-line workers, visual tracking, and flexible regimentation. Health care case studies illustrate each principle. The goal of this article is to provide a template for health care leaders to use in considering the implementation of the Lean management system or in assessing the current state of implementation in their organizations. PMID:23274021

  11. Analysis of promising sustainable renovation concepts

    DEFF Research Database (Denmark)

    Vanhoutteghem, Lies; Tommerup, Henrik M.; Svendsen, Svend;

    This report focuses on analyses of the most promising existing sustainable renovation concepts, i.e. full-service concepts and technical concepts, for single-family houses. As a basis for the analyses a detailed building stock analysis was carried out. Furthermore, as a basis a general working...... and contractors and the idea is to help the homeowner with design and decision making process. The building stock analysis shows that detached single-family houses account for large share of the total number of dwellings in all Nordic countries. Final energy use for space heating and hot water is in the range...... but built in the same way, using the same materials. Existing full-service renovation concepts in the Nordic countries have just recently entered the market and are not well established and their success is yet to be evaluated. The success is strongly influenced by the current renovation market...

  12. Halopentacenes: Promising Candidates for Organic Semiconductors

    Institute of Scientific and Technical Information of China (English)

    DU Gong-He; REN Zhao-Yu; GUO Ping; ZHENG Ji-Ming

    2009-01-01

    We introduce polar substituents such as F, Cl, Br into pentacene to enhance the dissolubility in common organic solvents while retaining the high charge-carrier mobilities of pentacene. Geometric structures, dipole moments,frontier molecule orbits, ionization potentials and electron affinities, as well as reorganization energies of those molecules, and of pentacene for comparison, are successively calculated by density functional theory. The results indicate that halopentacenes have rather small reorganization energies (< 0.2 eV), and when the substituents are in position 2 or positions 2 and 9, they are polarity molecules. Thus we conjecture that they can easily be dissolved in common organic solvents, and are promising candidates for organic semiconductors.

  13. Autism: Pathophysiology and Promising Herbal Remedies.

    Science.gov (United States)

    Bahmani, Mahmoud; Sarrafchi, Amir; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2016-01-01

    Autism is a comprehensive growth abnormality in which social skills, language, communication, and behavioral skills are developed with delay and as diversionary. The reasons for autism are unclear, but various theories of genetics, immunity, biological, and psychosocial factors have been proffered. In fact, autism is a complex disorder with distinct causes that usually co-occur. Although no medicine has been recognized to treat this disorder, pharmacological treatments can be effective in reducing its signs, such as self-mutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleeping disorders. Recently, complementary and alternative approaches have been considered to treat autism. Ginkgo biloba is one of the most effective plants with an old history of applications in neuropsychological disorders which recently is used for autism. The present review discusses the recent findings, pathophysiology, and etiology of autism and thereafter addresses the promising results of herbal remedies. PMID:26561063

  14. Targeting of Antibodies using Aptamers

    OpenAIRE

    Missailidis, Sotiris

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  15. Refolding Technologies for Antibody Fragments

    OpenAIRE

    Tsutomu Arakawa; Daisuke Ejima

    2014-01-01

    Refolding is one of the production technologies for pharmaceutical grade antibody fragments. Detergents and denaturants are primarily used to solubilize the insoluble proteins. The solubilized and denatured proteins are refolded by reducing the concentration of the denaturants or detergents. Several refolding technologies have been used for antibody fragments, comprising dilution, dialysis, solid phase solvent exchange and size exclusion chromatography, as reviewed here. Aggregation suppresso...

  16. Radiation induced promising mutants in Cowpea

    International Nuclear Information System (INIS)

    Cowpea (Vigna unguiculata L. Walp.) is an important legume crop of the tropics and subtropics of Asia, Africa and America. Breeding objectives in recent years have been to combine high yields with upright growth habit, bushy dwarf determinate plant type, early maturity and large seed size in addition to resistance to biotic and abiotic stresses. With a view to achieving these objectives and creating additional - variability, the seeds of an elite variety V-130 were irradiated with 200 Gy of gamma rays, and a number of morphological mutants were isolated. The mutants with desirable characters like erect growth habit, dwarf, large seed size, and high pod number were isolated in the M2 generation and studied further in subsequent generations for their yield potential and other characteristics. The dwarf plant mutant TCM 77-4, characterised by reduced plant height, bushy growth, large seed size and absence of tendril bred true when grown in rabi seasons, but behaved like parent in respect of growth habit in kharif season. It was far superior to the parent in respect of seed size in all the seasons. The mutant is envisaged to be the most suitable for rice fallows. Among the several promising mutants with large seed size, the mutant TCM 13-5 showed a test weight of 16.8 g against 8.8 g of the parent. A mutant with large pod number designated as TCM 121-8 showed promise with its very high yield, when grown in summer albeit with delayed maturity. Several mutants with maturity similar to that of the parent have shown higher seed yield. The variability generated through the radiation- induced mutation is being utilised for creating novel high yielding early maturing varieties of cowpea. (author)

  17. ANTISPERM ANTIBODIES IN VASOVASOSTOMY

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    1993-06-01

    Full Text Available Two hundred and forty patients, who had undergone vasectomy from 1977 to 1985 and subsequent vasovasostomy ,were studied for the presence of sperm-specific antibodies by using the Kibrick's gelatin agglutination test. The number of successful pregnancies and the presence of agglutination were also considered in this survey. Sixty-nine pregnancies occurred in total and agglutination was present in 49% out of 51% positive specimens by the Kibrick Test."nThe average sperm motility was slightly higher in the negative Kibrick group than in the positive Kibrick group. The obtained data indicated that there seems to be a relationship between the increased titers and percentage of agglutination in semen samples.

  18. Influenza-Specific Antibody-Dependent Phagocytosis

    Science.gov (United States)

    Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary; Jegaskanda, Sinthujan; Johnston, Angus; Rockman, Steven; Laurie, Karen; Barr, Ian; Reading, Patrick; Lichtfuss, Marit; Kent, Stephen J.

    2016-01-01

    Background Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized. Methods We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques. Results We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity in vitro. Conclusion We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection in vitro. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted. PMID:27124730

  19. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  20. Man-made antibodies and immunoconjugates with desired properties: function optimization using structural engineering

    International Nuclear Information System (INIS)

    The review outlines progress and problems in the design of non-natural antibodies for clinical applications over the past 10–15 years. The modular structure of natural antibodies and approaches to its targeted modifications and combination with other structural elements and effector molecules are considered. The review covers modern methods for immunoglobulin engineering and promising strategies for the creation and applications of monoclonal antibodies, their derivatives and analogues, including abzymes and scaffolds, oriented to the use in the diagnosis and targeted therapy of cancer and other socially significant diseases. The bibliography includes 225 references

  1. Epstein-Barr virus antibody test

    Science.gov (United States)

    EBV antibody test; EBV serology ... a lab, where a lab specialist looks for antibodies to the Epstein-Barr virus. In the first stages of an illness, little antibody may be detected. For this reason, the test ...

  2. Measurement of antibodies to tubulin by radioimmunoassay

    International Nuclear Information System (INIS)

    A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses. (Auth.)

  3. Antibodies - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit.

  4. Animal models of antineutrophil cytoplasm antibody-associated vasculitis.

    LENUS (Irish Health Repository)

    Salama, Alan D

    2012-01-01

    To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue.

  5. Novel electrokinetic approaches to improve purification processes with monoclonal antibodies

    OpenAIRE

    Faude, Alexander

    2009-01-01

    This work was focussed on mAb separations using cation exchange and hydrophobic interaction chromatography. Methods to accelerate long winded development strategies of purification processes with monoclonal antibodies were developed facilitated by further improvement of understanding the basic adsorption mechanisms of proteins on chromatographic resins. The new experimental electrokinetic methods introduced are zeta potential determination with proteins via laser light scattering and electro-...

  6. Genetically Modified Crops: Risks and Promise

    OpenAIRE

    Gordon Conway

    2000-01-01

    GM foods have the potential to provide significant benefits for developing countries. Over 800 million people are chronically undernourished, and 180 million children are severely underweight for their age. By 2020, there will be an extra two billion mouths to feed. Ecological approaches that underpin sustainable agriculture (e.g., integrated pest management) and participatory approaches that strengthen farmers' own experimentation and decision making are key. Biotechnology will be an es...

  7. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma.

    Science.gov (United States)

    van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben; Palumbo, Antonio; Gay, Francesca; Laubach, Jacob P; Malavasi, Fabio; Avet-Loiseau, Hervé; Mateos, Maria-Victoria; Sonneveld, Pieter; Lokhorst, Henk M; Richardson, Paul G

    2016-02-11

    Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents. Furthermore, although elotuzumab (anti-SLAMF7) has no single agent activity in advanced MM, randomized trials in relapsed/refractory MM have demonstrated significantly improved progression-free survival when elotuzumab is added to lenalidomide-dexamethasone or bortezomib-dexamethasone. Importantly, there has been no significant additive toxicity when these monoclonal antibodies are combined with other anti-MM agents, other than infusion-related reactions specific to the therapeutic antibody. Prevention and management of infusion reactions is important to avoid drug discontinuation, which may in turn lead to reduced efficacy of anti-MM therapy. Therapeutic antibodies interfere with several laboratory tests. First, interference of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products. Neutralization of the therapeutic CD38 antibody or CD38 denaturation on reagent red blood cells mitigates daratumumab interference with transfusion laboratory serologic tests. Finally, therapeutic antibodies may complicate flow cytometric evaluation of normal and neoplastic plasma cells, since the therapeutic antibody can affect the availability of the epitope for binding

  8. The importance of non-HLA antibodies in transplantation.

    Science.gov (United States)

    Zhang, Qiuheng; Reed, Elaine F

    2016-08-01

    The development of post-transplantation antibodies against non-HLA autoantigens is associated with rejection and decreased long-term graft survival. Although our knowledge of non-HLA antibodies is incomplete, compelling experimental and clinical findings demonstrate that antibodies directed against autoantigens such as angiotensin type 1 receptor, perlecan and collagen, contribute to the process of antibody-mediated acute and chronic rejection. The mechanisms that underlie the production of autoantibodies in the setting of organ transplantation is an important area of ongoing investigation. Ischaemia-reperfusion injury, surgical trauma and/or alloimmune responses can result in the release of organ-derived autoantigens (such as soluble antigens, extracellular vesicles or apoptotic bodies) that are presented to B cells in the context of the transplant recipient's antigen presenting cells and stimulate autoantibody production. Type 17 T helper cells orchestrate autoantibody production by supporting the proliferation and maturation of autoreactive B cells within ectopic tertiary lymphoid tissue. Conversely, autoantibody-mediated graft damage can trigger alloimmunity and the development of donor-specific HLA antibodies that can act in synergy to promote allograft rejection. Identification of the immunologic phenotypes of transplant recipients at risk of non-HLA antibody-mediated rejection, and the development of targeted therapies to treat such rejection, are sorely needed to improve both graft and patient survival. PMID:27345243

  9. Enediyne compounds - new promises in anticancer therapy.

    Science.gov (United States)

    Gredicak, Matija; Jerić, Ivanka

    2007-06-01

    Scientists of all kinds have long been intrigued by the nature, action and potential of natural toxins that possess exceptional antibacterial and anticancer activities. These compounds, named enediynes, are among the most effective chemotherapeutic agents known. Often compared with intelligent weapons, due to the unique structure and sophisticated mechanism by which they destroy double-helical DNA, enediyne antibiotics are nowadays the most promising leaders in the anticancer therapy. Apart from their diversity, enediyne compounds share some structural and functional similarities. One fragment of a structure is responsible for the recognition and transport, another part acts as molecular trigger while the third, reactive enediyne unit, undergoes Bergman cycloaromatization and causes DNA breakage. Members of the enediyne family are already in clinical use to treat various cancers, but more general use is limited by their complex structure, which makes them formidable targets for synthetic chemists. There are three main approaches in the design of new enediyne-related compounds: improvement of enediyne >warheadsenediynes, their mode of action and efforts undertaken to design artificial enediyne-related DNA cleaving agents. PMID:17507311

  10. Hyperthermia: Clinical promise and current challenges

    International Nuclear Information System (INIS)

    Local-regional hyperthermia (HT) when used in conjunction with radiation therapy (XRT), has been shown in numerous clinical trials to result in considerable improvement in response rates and local tumor control rates when compared with treatment by XRT alone. Although considerable progress has been made in understanding the biological basis for hyperthermia induced cytotoxicity and radiosensitization, additional research remains in establishing the optimal treatment schedules for the clinical utilization of HT-XRT. The number of HT treatments; the sequencing of HT and XRT; the frequency of administration of HT; and the ideal temperature-time parameters all remain to be better defined for the clinical setting. The role of tumor blood flow on the thermal distributions also warrants further investigation. In addition, considerable effort is needed to improve hyperthermia equipment in order to provide more uniform therapeutic temperature distributions (temperatures ≥42.5%C). Better heating equipment is particularly needed for the treatment of deep seeted tumors. Pertinent clinical literature will be presented summarizing the clinical promise of hyperthermia and the above mentioned clinical challenges

  11. ABOUT NEW PROMISING MATHEMATICAL TOOLS OF CONTROLLING

    Directory of Open Access Journals (Sweden)

    Orlov A. I.

    2015-11-01

    Full Text Available Based on an objective analysis, it must be noted that in the arsenal of managers, especially foreign ones, there is practically no fundamentally new methods and tools. However, promising mathematical and instrumental methods of controlling actively developed in our country. In the XXI century it developed a new paradigm of mathematical methods of economics and produced more than 10 books, developed in accordance with this paradigm. The new paradigm is based on the modern development of mathematics as a whole - on the system interval fuzzy math. The new paradigm offers tools used non-parametric statistics, which suggest that the distribution functions are arbitrary. In 1979 it was allocated one of the four major areas of modern applied statistics - statistics of objects of nonnumeric nature (statistics of non-numeric data, nonnumeric statistics. The other three - statistics of random variables, multivariate statistical analysis, statistics of random processes and time series. Statistics of objects of non-numeric nature is central to the modern mathematical methods of economics. On the basis of modern information-communication technologies we have developed a new economic theory - solidary information economy. New intellectual tools of controlling include an automated system-cognitive analysis (ASA and its software - the system of "Eidos". The systems approach to solving specific applications often requires going beyond the economy. Very important are the procedures for the introduction of innovative methods and tools

  12. Uterine transplantation: a promising surrogate to surrogacy?

    Science.gov (United States)

    Grynberg, Michael; Ayoubi, Jean-Marc; Bulletti, Carlo; Frydman, Rene; Fanchin, Renato

    2011-03-01

    Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. PMID:21401629

  13. Prospects, promises and properties of refractory intermetallics

    International Nuclear Information System (INIS)

    Extensive research activity, over the last 15 years, has been conducted on structure/property relationships and processing of intermetallic compounds for high temperature use. Progress has been made in improving a number of properties of these compounds; however, the demanding balance of properties required (high strength, good strength retention at temperatures exceeding 1,000 C, low density, damage tolerance at ambient temperatures, good creep and stress rupture characteristics and environmental stability at high temperatures) are not likely to be achieved in a monolithic (single phase) compound. Initial work on intermetallic matrix composites has proven to be quite promising. It has already been shown that compounds, brittle at room temperature, may be toughened by the inclusion of appropriate reinforcements, either strong or tough and ductile. Both artificial and natural or in-situ composite fabrication techniques have been used to manufacture these composite systems. The properties of two specific intermetallic matrix composite systems, NiAl/Al2O3 and Cr2Nb/Nb are summarized to elucidate their strengths, weaknesses and potential. Candidate composite systems are also discussed along with the rationale behind their selection

  14. Detection of newly antibody-defined epitopes on HLA class I alleles reacting with antibodies induced during pregnancy.

    Science.gov (United States)

    Duquesnoy, R J; Hönger, G; Hösli, I; Marrari, M; Schaub, S

    2016-08-01

    The determination of HLA mismatch acceptability at the epitope level can be best performed with epitopes that have been verified experimentally with informative antibodies. The website-based International Registry of HLA Epitopes (http://www.epregistry.com.br) has a list of 81 antibody-verified HLA-ABC epitopes but more epitopes need to be added. Pregnancy offers an attractive model to study antibody responses to mismatched HLA epitopes which can be readily determined from the HLA types of child and mother. This report describes a HLAMatchmaker-based analysis of 16 postpregnancy sera tested in single HLA-ABC allele binding assays. Most sera reacted with alleles carrying epitopes that have been antibody-verified, and this study focused on the reactivity of additional alleles that share other epitopes corresponding to eplets and other amino acid residue configurations. This analysis led in the identification of 16 newly antibody-defined epitopes, seven are equivalent to eplets and nine correspond to combinations of eplets in combination with other nearby residue configurations. These epitopes will be added to the repertoire of antibody-verified epitopes in the HLA Epitope Registry. PMID:27312793

  15. RDoC: Translating promise into progress.

    Science.gov (United States)

    Patrick, Christopher J; Hajcak, Greg

    2016-03-01

    As highlighted by articles in the current special issue, the RDoC initiative holds promise for advancing understanding of mental health problems. However, the initiative is at its early stages and it remains unclear what level of progress can be achieved and how quickly. In this closing article, we identify major challenges facing RDoC and propose concrete approaches to addressing these challenges, including (a) clearer specification of clinical problems for study, with use of symptom dimensions from integrative dimensional models of psychopathology as provisional, modifiable referents; (b) encouragement of research on a distinct set of traits corresponding to process constructs from the RDoC matrix-those represented across animal, child temperament, and adult personality literatures-to serve as interfaces between matrix constructs and clinical problems; (c) an emphasis in the near term on use of proximal units of analysis in RDoC studies-in particular, on physiological, behavioral, and self-report measures of matrix constructs (examined as states or traits, or both); (d) inclusion of a clear ontogenetic-developmental component in RDoC research projects; (e) routine analysis of the psychometric properties of nonreport (e.g., physiological, task-behavioral) variables, including systematic evaluation of their reliability and convergent-discriminant validity; (f) modification of existing grant review criteria to prioritize replication and synergy in RDoC investigative work; and (g) creation of a cumulative data network system (RDoC-DataWeb) to encourage and facilitate coordination of research efforts across RDoC research groups. PMID:26877135

  16. Secukinumab: a promising therapeutic option in spondyloarthritis.

    Science.gov (United States)

    Maldonado-Ficco, Hernan; Perez-Alamino, Rodolfo; Maldonado-Cocco, José A

    2016-09-01

    Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety. PMID:27437696

  17. The promise of innovation: Nuclear energy horizons

    International Nuclear Information System (INIS)

    The 21st century promises the most open, competitive, and globalized markets in human history, as well as the most rapid pace of technological change ever. For nuclear energy, as any other, that presents challenges. Though the atom now supplies a good share of world electricity, its share of total energy is relatively small, anywhere from four to six per cent depending on how it is calculated. And, while energy is most needed in the developing world, four of every five nuclear plants are in industrialized countries. Critical problems that need to be overcome are well known - high capital costs for new plants, and concerns over proliferation risks and safety, (including safety of waste disposal) stand high among them. The IAEA and other programmes are confronting these problems through ambitious initiatives involving both industrialized and developing countries. They include the collaborative efforts known as the Generation-IV International Forum (GIF) and the IAEA International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). They use ideas, results and the best experiences from today's research and development tools and advanced types of nuclear energy systems to meet tomorrow's challenges. Though the market often decides the fate of new initiatives, the market is not always right for the common good. Governments, and the people that influence them, play an indispensable role in shaping progress in energy fields for rich and poor countries alike. They shoulder the main responsibilities for fundamental science, basic research, and long-term investments. For energy in particular, government investment and support will prove instrumental in the pace of innovation toward long-term options that are ready to replace limited fossil fuel supplies, and respond to the growing premium put on clean energy alternatives. Yet governments cannot go it alone. The challenges are too diverse and complex, and public concerns - about proliferation or safety - go beyond

  18. Radioimmunoassay for anticollagen-antibodies using 14C-labelled collagen

    International Nuclear Information System (INIS)

    A sensitive radioimmunoassay for anticollagen antibodies is described. 14C-labelled human acid-soluble collagen of high specific activity (5 x 106 dpm/mg) is used as antigen either in native or denatured state. Experimentally induced anticollagen antibodies or RA synovial fluids containing antibodies to collagen are reacted with the labelled antigen. The immune complexes formed are precipitated with goat antiserum to rabbit globulins ('second antibody'). A systematic investigation of the labelled collagen in regard to cleavage by enzymes, fibril formation and specificity showed that no gross alteration had been caused by the labelling procedure. The assay furnishes information on the avidity, specificity and immunoglobulin class of experimental or pathological anticollagen antibodies. It can also be used as sensitive assay for collagen in biological fluids

  19. Antibody fragments: Hope and hype

    OpenAIRE

    Nelson, Aaron L

    2010-01-01

    The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variabl...

  20. Functional effects of anticardiolipin antibodies.

    Science.gov (United States)

    Harris, E N; Pierangeli, S S

    1996-10-01

    The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important. PMID:8902763

  1. The antineutrophil antibody in uveitis.

    OpenAIRE

    Young, D W

    1991-01-01

    Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular ...

  2. Interfacial metal and antibody recognition

    OpenAIRE

    Zhou, Tongqing; Hamer, Dean H.; Hendrickson, Wayne A.; Sattentau, Quentin J.; Kwong, Peter D.

    2005-01-01

    The unique ligation properties of metal ions are widely exploited by proteins, with approximately one-third of all proteins estimated to be metalloproteins. Although antibodies use various mechanisms for recognition, to our knowledge, none has ever been characterized that uses an interfacial metal. We previously described a family of CD4-reactive antibodies, the archetype being Q425. CD4:Q425 engagement does not interfere with CD4:HIV-1 gp120 envelope glycoprotein binding, but it blocks subse...

  3. Pyoderma gangrenosum and anticardiolipin antibody

    Directory of Open Access Journals (Sweden)

    de Godoy Jose Maria

    2006-01-01

    Full Text Available Pyoderma gangrenosum (PG is a rare ulceronecrotic inflammatory cutaneous disorder and is frequently associated with systemic diseases. The authors report a 22-year-old male patient with pyoderma gangrenosum, thrombosis of both popliteal arteries, ischemic stroke and seropositivity for anticardiolipin antibody. Despite intravenous treatment with antibiotics, corticosteroid and heparin, pyoderma gangrenosum caused necrosis of his right lower limb which resulted in amputation. It was concluded that the anticardiolipin antibody may have contributed to the gravity of this case.

  4. Efficient method to optimize antibodies using avian leukosis virus display and eukaryotic cells.

    Science.gov (United States)

    Yu, Changming; Pike, Gennett M; Rinkoski, Tommy A; Correia, Cristina; Kaufmann, Scott H; Federspiel, Mark J

    2015-08-11

    Antibody-based therapeutics have now had success in the clinic. The affinity and specificity of the antibody for the target ligand determines the specificity of therapeutic delivery and off-target side effects. The discovery and optimization of high-affinity antibodies to important therapeutic targets could be significantly improved by the availability of a robust, eukaryotic display technology comparable to phage display that would overcome the protein translation limitations of microorganisms. The use of eukaryotic cells would improve the diversity of the displayed antibodies that can be screened and optimized as well as more seamlessly transition into a large-scale mammalian expression system for clinical production. In this study, we demonstrate that the replication and polypeptide display characteristics of a eukaryotic retrovirus, avian leukosis virus (ALV), offers a robust, eukaryotic version of bacteriophage display. The binding affinity of a model single-chain Fv antibody was optimized by using ALV display, improving affinity >2,000-fold, from micromolar to picomolar levels. We believe ALV display provides an extension to antibody display on microorganisms and offers virus and cell display platforms in a eukaryotic expression system. ALV display should enable an improvement in the diversity of properly processed and functional antibody variants that can be screened and affinity-optimized to improve promising antibody candidates. PMID:26216971

  5. Green and social bonds - A promising tool

    International Nuclear Information System (INIS)

    Issues of green bonds, socially responsible bonds and climate bonds are on the rise. Novethic estimates that some Euro 5 billion in such bonds has been issued since the start of 2013 by development banks, the main issuers of this type of debt. The figure is equal to over half of their total issues since 2007. Including local authorities, corporations and banks, a total Euro 8 billion of these bonds has been issued thus far in 2013. Given the size of the bond market, which the OECD estimated at Euro 95,000 billion in 2011, green and social bonds are still something of a niche but have strong growth potential. A number of large issues, from Euro 500 million to Euro 1 billion, were announced at the end of the year. Unlike conventional bonds, green and social bonds are not intended to finance all the activities of the issuer or refinance its debt. They serve instead to finance specific projects, such as producing renewable energy or adapting to climate change, the risk of which is shouldered by the issuer. This makes them an innovative instrument, used to earmark investments in projects with a direct environmental or social benefit rather than simply on the basis of the issuer's sustainable development policy. With financing being sought for the ecological transition, green and social bonds are promising instruments, sketching out at global level the shape of tools adapted to the financing of a green economy. On the strength of these advantages, the interest of responsible investors - the main target of green and social bond issuers - is growing fast. Judging by issuer press releases and the most commonly used currencies, the main subscribers today are US investors, among them CalSTRS and fund managers like Calvert Investment Management and Trillium Asset Management. European asset owners are also starting to focus on green and social bonds. A Novethic survey shows that 13% of them have already subscribed to such an issue or plan to do so. The present study

  6. Antibodies to watch in 2014.

    Science.gov (United States)

    Reichert, Janice M

    2014-01-01

    Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed. PMID:24284914

  7. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo

    2014-10-09

    SUMMARY: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity into a suitable human template. Unfortunately, this procedure may results in a partial or complete loss of affinity of the grafted molecule that can be restored by back-mutating some of the residues of human origin to the corresponding murine ones. This trial-and-error procedure is hard and involves expensive and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http://www.biocomputing.it/tabhu CONTACT: anna.tramontano@uniroma1.it, pierpaolo.olimpieri@uniroma1.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  8. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  9. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author)

  10. Radioimmunoguided surgery using monoclonal antibody

    International Nuclear Information System (INIS)

    The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery

  11. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x107 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x107 spleen cells to 1x106 myeloma cells (ratio 10:1). Centrifuge

  12. Stem Cell Therapy Shows Promise Against Heart Failure

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158122.html Stem Cell Therapy Shows Promise Against Heart Failure A second ... 4, 2016 MONDAY, April 4, 2016 (HealthDay News) -- Stem cell therapy shows promise for people battling heart failure, ...

  13. Mechanisms of resistance to HER family targeting antibodies

    International Nuclear Information System (INIS)

    The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.

  14. Mechanisms of resistance to HER family targeting antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Wheeler, Deric L., E-mail: dlwheeler@wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States)

    2010-04-15

    The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.

  15. The NPT regime: Progress and promises

    International Nuclear Information System (INIS)

    Full text: Thesis. The 'NPT regime' has arrived at a fateful crossroads. Though extended indefinitely in 1995, its future is my no means secure. The future 'progress' of this treaty will depend upon whether the 'promises' of its States parties are fully implemented and, eventually, upon the treaty's success in achieving fully universal membership. Challenges The treaty faces many short-term and longer-term challenges: Short term - The first Preparatory Committee meeting for the 2005 Review Conference will meet next year. NNWS will want to see some evidence of progress on nuclear disarmament (Art. VI), along the lines prescribed in the 13 'practical steps' agreed at the last Review Conference. Yet progress has been set back by: uncertainties over the future of the ABM Treaty; the failure of START II and the CTBT to enter into force; the lack of a FISMAT treaty and a treaty establishing a NWFZ in Central Asia; continued qualitative improvements in nuclear weapons; hints that nuclear testing may one day resume; the persistence of doctrines of first-use, pre-emptive use, and use against states that use CBW. Other compliance-related questions will arise over safeguards (e.g. the inability of the IAEA to conduct inspections in the DPRK; signs of a breakdown of the norm of full-scope IAEA safeguards, e.g. in South Asia). There are also concerns over the implementation of non-proliferation commitments (e.g. persisting allegations about nuclear weapon programmes in existing NNWS). The terrorist attacks in New York and Washington, D.C. on 11 September should also serve as a reminder of the new terrorist dangers relating to the possible use of weapons of mass destruction and unorthodox delivery systems. Longer term - Selectivity in the enforcement of NPT norms; unilateralism; IAEA funding uncertainties and shortfalls; difficulties in reaching universal membership (India, Pakistan, and Israel); continuing compliance problems with respect to both non-proliferation and

  16. The Promise of Wave Power (Invited)

    Science.gov (United States)

    Brekken, T.

    2010-12-01

    The solutions to today's energy challenges need to be explored through alternative, renewable and clean energy sources to enable diverse energy resource plans. An extremely abundant and promising source of energy exists in the world's oceans: it is estimated that if 0.2 % of the oceans' untapped energy could be harnessed, it could provide power sufficient for the entire world. Ocean energy exists in the forms of wave, tidal, marine currents, thermal (temperature gradient) and salinity. Among these forms, significant opportunities and benefits have been identified in the area of ocean wave energy extraction, i.e., harnessing the motion of the ocean waves, and converting that motion into electrical energy. Ocean wave energy refers to the kinetic and potential energy in the heaving motion of ocean waves. Wave energy is essentially concentrated solar energy (as is wind energy). The heating of the earth’s surface by the sun (with other complex processes) drives the wind, which in turn blows across the surface of the ocean to create waves. At each stage of conversion, the power density increases. Ocean wave power offers several attractive qualities, including high power density, low variability, and excellent forecastability. A typical large ocean wave propogates at around 12 m/s with very little attenuation across the ocean. If the waves can be detected several hundred kilometers off shore, there can be 10 hours or more of accurate forecast horizon. In fact, analysis has shown good forecast accuracy up to 48 hours in advance. Off the coast Oregon, the yearly average wave power is approximately 30 kW per meter of crestlength (i.e., unit length transverse to the direction of wave propagation and parallel to the shore.) This compares very favorably with power densities of solar and wind, which typically range in the several hundreds of Watts per square meter. Globally, the wave energy resource is stronger on the west coasts of large landmasses and increases in strength

  17. Prosecuting the Leaders: Promises, Politics and Practicalities

    Directory of Open Access Journals (Sweden)

    Robert Cryer

    2009-02-01

    Full Text Available Given recent developments in relation to the prosecution of international crimes,  it might be thought that one of the last bastions of sovereignty has been breached, and international criminal law has not only entrenched itself in international law. Indeed further to this, it has assumed a supranational position that stands entirely above States, promising justice for all and as a trump card over depredations committed in the name of State sovereignty. After all, Charles Taylor from Liberia is standing trial before the Special Court for Sierra Leone, Slobodan Milošević only escaped judgment by the International Criminal Tribunal for the former

  18. Radiolabelling of monoclonal antibodies with technetium-99 m via metallothionein

    International Nuclear Information System (INIS)

    Metallothionein (MT), a small cysteine-rich protein, was used as a bifunctional chelating agent in the radiolabelling of monoclonal antibodies with Tc-99m. The efficiency of the conjugation reaction of MT with antibodies (Ab) was found as 58%. The yield of radiolabelling of Tc-99m to MT-Ab by reduction method was higher than 90%, while the unspecific radiolabelling occurred less than 10%. The Tc-99m-MT-Ab has proven to be satisfactory stable in Vitro in the presence of a couple of strong chelating agents. The preliminary biological experimental results in tumor-bearing nude mice indicated that the Tc-99m-labelled anti-colorectal carcinoma monoclonal antibody 2C10 had strong affinity toward tumor and was stable in vivo

  19. Production of recombinant antibodies using bacteriophages

    OpenAIRE

    Shukra, A. M.; Sridevi, N. V.; Dev Chandran,; Kapil Maithal,

    2014-01-01

    Recombinant antibody fragments such as Fab, scFv, diabodies, triabodies, single domain antibodies and minibodies have recently emerged as potential alternatives to monoclonal antibodies, which can be engineered using phage display technology. These antibodies match the strengths of conventionally produced monoclonal antibodies and offer advantages for the development of immunodiagnostic kits and assays. These fragments not only retain the specificity of the whole monoclonal ...

  20. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  1. OptMAVEn – A New Framework for the de novo Design of Antibody Variable Region Models Targeting Specific Antigen Epitopes

    OpenAIRE

    Li, Tong; Pantazes, Robert J; Maranas, Costas D.

    2014-01-01

    Antibody-based therapeutics provides novel and efficacious treatments for a number of diseases. Traditional experimental approaches for designing therapeutic antibodies rely on raising antibodies against a target antigen in an immunized animal or directed evolution of antibodies with low affinity for the desired antigen. However, these methods remain time consuming, cannot target a specific epitope and do not lead to broad design principles informing other studies. Computational design method...

  2. The Promise of the Anti-Idiotype Concept

    OpenAIRE

    ThomasKieber-Emmons; AnastasPashov; RamachandranMurali; HeinzKohler

    2012-01-01

    A basic tenet of antibody-based immunity is their specificity to antigenic determinates from foreign pathogen products to abnormal cellular components such as in cancer. However, an antibody has the potential to bind to more than one determinate, be it an antigen or another antibody. These observations led to the idiotype network theory (INT) to explain immune regulation, which has wax and waned in enthusiasm over the years. A truer measure of the impact of the INT is in terms of the ideas th...

  3. Genetically Modified Crops: Risks and Promise

    Directory of Open Access Journals (Sweden)

    Gordon Conway

    2000-07-01

    Full Text Available GM foods have the potential to provide significant benefits for developing countries. Over 800 million people are chronically undernourished, and 180 million children are severely underweight for their age. By 2020, there will be an extra two billion mouths to feed. Ecological approaches that underpin sustainable agriculture (e.g., integrated pest management and participatory approaches that strengthen farmers' own experimentation and decision making are key. Biotechnology will be an essential partner, if yield ceilings are to be raised, if crops are to be grown without excessive reliance on pesticides, and if farmers on less favored lands are to be provided with crops that are resistant to drought and salinity, and that can use nitrogen and other nutrients more efficiently. Over the past 10 years, in addition supporting ecological approaches, the Rockefeller Foundation has funded the training of some 400 developing-country scientists in the techniques of biotechnology. Most of the new crop varieties are the result of tissue culture and marker-aided selection. The Foundation also supports the production of genetically engineered rices, including a new rice engineered for beta carotene (the precursor of Vitamin A in the grain. Some specific steps can be taken by Monsanto that would improve acceptance of plant biotechnology in both the developing and the industrialized worlds: label; disavow gene protection (terminator systems; phase out the use of antibiotic resistance markers; agree (with big seed companies to use the plant variety protection system, rather than patents, in developing countries; establish an independently administered fellowship program to train developing-country scientists in crop biotechnology, biosafety, and intellectual property; donate useful technologies to developing countries; agree to share financial rewards from intellectual property rights on varieties such as basmati or jasmine rice with the countries of origin; and

  4. Novel Antibody-Based Proteins for Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fuenmayor, Jaheli; Montaño, Ramon F., E-mail: jfuenmay@ivic.gob.ve [Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas. Caracas, 1020-A (Venezuela, Bolivarian Republic of)

    2011-08-19

    The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.

  5. Novel Antibody-Based Proteins for Cancer Immunotherapy

    International Nuclear Information System (INIS)

    The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future

  6. Radiosensitivity of antibody responses and radioresistant secondary tetanus antitoxin responses

    International Nuclear Information System (INIS)

    Primary tetanus antitoxin responses were increasingly repressed in mice when gamma radiation doses of 100 to 400 rads were delivered by whole-body exposure prior to immunization with fluid tetanus toxoid (FTT). Nearly normal secondary antitoxin responses were obtained in mice exposed to 600 rads of gamma radiation 4 days after secondary antigenic stimulation with FTT. A rapid transition from radiosensitivity of the antibody-forming system on days 1 to 3 was followed by relative radioresistance on day 4 after the booster injection of toxoid. Studies on lymphoid cellular kinetics in popliteal lymph nodes after injection of 3H--thymidine (3H--TdR) and incorporation of 3H--L-histidine into circulating antitoxin were carried out. Analysis of tritium radioactivity in antigen--antibody precipitates of serums 2 hr after injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after the booster in nonirradiated controls and about day 12, i.e., 8 days after irradiation, in experimental mice. The shift from radiosensitivity to relative radioresistance was attributed to a marked peak of plasma-cell proliferation in the medulla of lymph nodes on day 3. Many medullary plasma cells survived and continued to proliferate after exposure to radiation. Germinal centers were destroyed by radiation within 1 day. Since antibody formation continued after exposure to radiation and after the loss of germinal centers, this supports the view that germinal-center cells were involved more in the generation of memory cells than in antibody synthesis

  7. Antibodies to watch in 2016.

    Science.gov (United States)

    Reichert, Janice M

    2016-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by the antibody therapeutics discussed in this perspective, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future. *See Note added in proof for updates through December 31, 2015. PMID:26651519

  8. Scientists find promising predictor of HPV-related oropharynx cancer

    Science.gov (United States)

    Researchers have found that antibodies against the human papillomavirus (HPV) may help identify individuals who are at greatly increased risk of HPV-related cancer of the oropharynx, which is a portion of the throat that contains the tonsils.

  9. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    Science.gov (United States)

    Goel, Aimee

    2016-01-01

    Spinal cord injury (SCI) remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

  10. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    Directory of Open Access Journals (Sweden)

    Aimee Goel

    2016-01-01

    Full Text Available Spinal cord injury (SCI remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

  11. Stem cell therapy in spinal cord injury: Hollow promise or promising science?

    Science.gov (United States)

    Goel, Aimee

    2016-01-01

    Spinal cord injury (SCI) remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI. PMID:27217662

  12. Theoretical analysis of antibody targeting of tumor spheroids: importance of dosage for penetration, and affinity for retention.

    Science.gov (United States)

    Graff, Christilyn P; Wittrup, K Dane

    2003-03-15

    The interplay among antibody/antigen binding kinetics, antibody diffusion, and antigen metabolic turnover together determines the depth of penetration of antitumor antibodies into prevascular tumor spheroid cell clumps. A sharp boundary between an outer shell of bound high-affinity antibody and an inner antibody-free core has been previously observed and mathematically modeled and was termed the "binding site barrier." We show here that this process is well described by a simplified shrinking core model wherein binding equilibration is much more rapid than diffusion. This analysis provides the following experimentally testable predictions: (a) the binding site barrier is a moving boundary whose velocity is proportional to the time integral of antibody concentration at the spheroid surface (i.e. plasma antibody AUC); (b) the velocity of this moving boundary is independent of binding affinity, if the affinity is sufficiently high to strongly favor antibody/antigen complex formation at prevailing antibody concentrations; and (c) maximum tumor retention is achieved when the antibody/antigen dissociation rate approaches the rate of antigen metabolic turnover. The consistency of these predictions with published experimental results is demonstrated. The shrinking core model provides a simple analytic relationship predicting the effects of altered antibody pharmacokinetics, antibody molecular weight, antigen turnover rate, antigen expression level, and micrometastasis size on antibody penetration and retention. For example, a formula is provided for predicting the bolus dose necessary to accomplish tumor saturation as a function of antibody and tumor properties. Furthermore, this analysis indicates certain attributes necessary for an optimal tumor targeting agent. PMID:12649189

  13. Monolayer MXenes: promising half-metals and spin gapless semiconductors

    Science.gov (United States)

    Gao, Guoying; Ding, Guangqian; Li, Jie; Yao, Kailun; Wu, Menghao; Qian, Meichun

    2016-04-01

    Half-metals and spin gapless semiconductors are promising candidates for spintronic applications due to the complete (100%) spin polarization of electrons around the Fermi level. Based on recent experimental and theoretical findings of graphene-like monolayer transition metal carbides and nitrides (also known as MXenes), we demonstrate using first-principles calculations that monolayers Ti2C and Ti2N exhibit nearly half-metallic ferromagnetism with the magnetic moments of 1.91 and 1.00μB per formula unit, respectively, while monolayer V2C is a metal with unstable antiferromagnetism, and monolayer V2N is a nonmagnetic metal. Interestingly, under a biaxial strain, there is a phase transition from a nearly half-metal to truly half-metal, spin gapless semiconductor, and metal for monolayer Ti2C. Monolayer Ti2N is still a nearly half-metal under a suitable biaxial strain. Large magnetic moments can be induced by the biaxial tensile and compressive strains for monolayer V2C and V2N, respectively. We also show that the structures of these four monolayer MXenes are stable according to the calculated formation energy and phonon spectrum. Our investigations suggest that, unlike monolayer graphene, monolayer MXenes Ti2C and Ti2N without vacancy, doping or external electric field exhibit intrinsic magnetism, especially the half-metallic ferromagnetism and spin gapless semiconductivity, which will stimulate further studies on possible spintronic applications for new two-dimensional materials of MXenes.

  14. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  15. Antisperm antibodies and in vitro fertilization.

    Science.gov (United States)

    Janssen, H J; Bastiaans, B A; Goverde, H J; Hollanders, H M; Wetzels, A A; Schellekens, L A

    1992-08-01

    The purpose of this study was to investigate the influence of antisperm antibodies in the male, the female, or both partners on the outcome of in vitro fertilization treatment. The results in terms of ongoing pregnancies in the male and female antibody-positive group were the same as in the antibody-negative group. In the double antibody-positive group two of the three patients became pregnant. When high levels of antisperm antibodies were present on the spermatozoa, the fertilization rate was significantly reduced. In the female positive group no clear relationship between the antibody titer and the fertilization percentage could be detected. Abnormal semen quality was responsible for a much lower fertilization rate than the presence of antibodies. The conclusion of this study is that in vitro fertilization provides an equal change of conception in couples with antisperm antibodies in comparison with couples with no antibodies if the other semen parameters are normal. PMID:1472812

  16. Remembering antibodies coming of age.

    Science.gov (United States)

    Melchers, Fritz

    2016-01-01

    Fifty years ago, Norbert Hilschmann discovered that antibodies have variable immunoglobulin domains to bind antigens, and constant domains to carry out effector functions in the immune system. Just as this happened, the author of this perspective entered the field of immunology. Ten years later, the genetic basis of antibody variability was discovered by Susumu Tonegawa and his colleagues at the Basel Institute for Immunology, where the author had become a scientific member. At the same time, Georges Köhler, a former graduate student of the author's at the Basel Institute, invented with Cesar Milstein at the Laboratory of Molecular Biology in Cambridge, England, the method to produce monoclonal antibodies. The author describes here his memories connected to these three monumental, paradigm-changing discoveries, which he observed in close proximity. PMID:27144253

  17. Molecular-specific urokinase antibodies

    Science.gov (United States)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  18. Target-selective homologous recombination cloning for high-throughput generation of monoclonal antibodies from single plasma cells

    OpenAIRE

    Isobe Masaharu; Yoshioka Megumi; Kurosawa Nobuyuki

    2011-01-01

    Abstract Background Molecular cloning of functional immunoglobulin genes from single plasma cells is one of the most promising technologies for the rapid development of monoclonal antibody drugs. However, the proper insertion of PCR-amplified immunoglobulin genes into expression vectors remains an obstacle to the high-throughput production of recombinant monoclonal antibodies. Results We developed a single-step cloning method, target-selective homologous recombination (TS-HR), in which PCR-am...

  19. Antibody Response to Pneumocystis jirovecii

    OpenAIRE

    Daly, Kieran R.; Huang, Laurence; Morris, Alison; Koch, Judy; Crothers, Kristina; Levin, Linda; Eiser, Shary; Satwah, Supriya; Zucchi, Patrizia; Walzer, Peter D.

    2006-01-01

    We conducted a prospective pilot study of the serologic responses to overlapping recombinant fragments of the Pneumocystis jirovecii major surface glycoprotein (Msg) in HIV-infected patients with pneumonia due to P. jirovecii and other causes. Similar baseline geometric mean antibody levels to the fragments measured by an ELISA were found in both groups. Serum antibodies to MsgC in P. jirovecii patients rose to a peak level 3–4 weeks (p50 cells/μL and first episode of pneumocystosis were the ...

  20. Radioimmunotherapy with engineered antibody fragments

    International Nuclear Information System (INIS)

    Authors have developed and begun evaluating radiometal-chelated (213Bi) engineered antibody fragments as radioimmunotherapy agents that target the HER2/neu (c-erbB-2) antigen. The diabody format was found to have 40-fold greater affinity for HER2/neu and to be associated with significantly greater tumor localization than is achieved with scFv molecule. It is shown that short-lived isotopes like 213Bi would be most effective when used in conjunction with antibodies that targeted diffuse malignancies (leukemia or lymphoma) or when used for very rapid pretargeted radioimmunotherapy application in which the radioisotope is conjugated to a very small ligand

  1. Antibody sensed protein surface conformation

    Directory of Open Access Journals (Sweden)

    Scott R. Schricker

    2011-12-01

    Full Text Available An antibody-modified atomic force microscope (AFM tip was used to detect conformational changes of fibronectin deposited on a poly(methyl methacrylate/poly(acrylic acid block copolymer compared to PMMA and a random poly(methyl methacrylate/poly(acrylic acid copolymer with an identical chemical composition. Based on the antibody-protein adhesive force maps and phase imaging, it was found that the nanomorphology of the triblock copolymer induces the desired conformation of fibronectin. This finding demonstrates that block copolymer nanomorphology can be used to regulate protein conformation and potentially cellular response.

  2. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A; Thompson, Vicki S

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  3. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  4. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S

    2010-04-13

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  5. Antibody profiling sensitivity through increased reporter antibody layering

    International Nuclear Information System (INIS)

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  6. Efficient, chemoselective synthesis of immunomicelles using single-domain antibodies with a C-terminal thioester

    Directory of Open Access Journals (Sweden)

    Raats Jos MH

    2009-07-01

    Full Text Available Abstract Background Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL. However, current methods to generate antibody fragments with C-terminal thioesters require cumbersome refolding procedures, effectively preventing application of NCL for antibody-mediated targeting and molecular imaging. Results Targeting to the periplasm of E. coli allowed efficient production of correctly-folded single-domain antibody (sdAb-intein fusions proteins. On column purification and 2-mercapthoethanesulfonic acid (MESNA-induced cleavage yielded single-domain antibodies with a reactive C-terminal MESNA thioester in good yields. These thioester-functionalized single-domain antibodies allowed synthesis of immunomicelles via native chemical ligation in a single step. Conclusion A novel procedure was developed to obtain soluble, well-folded single-domain antibodies with reactive C-terminal thioesters in good yields. These proteins are promising building blocks for the chemoselective functionalization via NCL of a broad range of nanoparticle scaffolds, including micelles, liposomes and dendrimers.

  7. Initial study with Tc99m antigranulocyte antibody (MAK-47) in detection sources of infection

    International Nuclear Information System (INIS)

    Antigranulocytes antibodies (AGAB) are antibodies directed against glycoprotein on the surface of granulocytes and as such provides in vivo cell labelling. They are easily labelled with Tc99m and comes a one step labelling technique. 20 patients have been studied 1 h and 4-6 hours after administration of 200 MBq of Tc99m AGAB (MAK-47). Less then 0.5 mg of antibody was given to each patients. Sites of uptake and outside of the reticular-endothelial system were reported as showing positive accumulation. Clinical results were confirmed by microbiological, pathological examinations, clinical follow-up and autopsy. There were 8 patients who had sites of infection confirmed by additional examination. All patients were visualized by Tc99m AGAB (MAK-47). There were 4 cases of osteomyelitis and septic arthritis and 4 cases of focal intra-abdominal infection. Two patients had uptake in non-infected/inflammatory arthritis, both in the knee. The remaining patients had true negative studies. The diagnostic accuracy of this study was as follows: sensitivity 100%, specificity 83%, positive predictive value (PPV) was 80% and negative predictive value (NPV) was 100%. Antigranulocyte antibody (MAK-47) seems to by promising tool in detecting focal infection in bone and soft tissue, except physiological accumulation in some parts of the body. It should be considered that antibodies can have non-specific uptake in non-infected, inflammation sites. It is easy to use and no had allergic reaction and HAMA antibody (human antimouse antibody). (author)

  8. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Tal Noy-Porat

    2016-03-01

    Full Text Available Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1 that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication.

  9. Harnessing the protective potential of HIV-1 neutralizing antibodies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    S Abigail Smith

    2016-01-01

    Full Text Available Recent biological, structural, and technical advances are converging within the HIV-1 vaccine field to harness the power of antibodies for prevention and therapy. Numerous monoclonal antibodies with broad neutralizing activity against diverse HIV-1 isolates have now been identified, revealing at least five sites of vulnerability on the envelope (Env glycoproteins. While there are practical and technological barriers blocking a clear path from broadly neutralizing antibodies (bNAb to a protective vaccine, this is not a dead end. Scientists are revisiting old approaches with new technology, cutting new trails through unexplored territory, and paving new roads in the hopes of preventing HIV-1 infection. Other promising avenues to capitalize on the power of bNAbs are also being pursued, such as passive antibody immunotherapy and gene therapy approaches. Moreover, non-neutralizing antibodies have inhibitory activities that could have protective potential, alone or in combination with bNAbs. With a new generation of bNAbs, and a clinical trial that associated antibodies with reduced acquisition, the field is closer than ever to developing strategies to use antibodies against HIV-1.

  10. Antibody humanization by molecular dynamics simulations-in-silico guided selection of critical backmutations.

    Science.gov (United States)

    Margreitter, Christian; Mayrhofer, Patrick; Kunert, Renate; Oostenbrink, Chris

    2016-06-01

    Monoclonal antibodies represent the fastest growing class of biotherapeutic proteins. However, as they are often initially derived from rodent organisms, there is a severe risk of immunogenic reactions, hampering their applicability. The humanization of these antibodies remains a challenging task in the context of rational drug design. "Superhumanization" describes the direct transfer of the complementarity determining regions to a human germline framework, but this humanization approach often results in loss of binding affinity. In this study, we present a new approach for predicting promising backmutation sites using molecular dynamics simulations of the model antibody Ab2/3H6. The simulation method was developed in close conjunction with novel specificity experiments. Binding properties of mAb variants were evaluated directly from crude supernatants and confirmed using established binding affinity assays for purified antibodies. Our approach provides access to the dynamical features of the actual binding sites of an antibody, based solely on the antibody sequence. Thus we do not need structural data on the antibody-antigen complex and circumvent cumbersome methods to assess binding affinities. © 2016 The Authors Journal of Molecular Recognition Published by John Wiley & Sons Ltd. PMID:26748949

  11. Towards topic maps for a promise theory based configuration management

    OpenAIRE

    2009-01-01

    Knowledge management is the major challenge of today. Capturing expert information in a knowledge base that allows non-experts to locate it requires a carefully designed knowledge model. We attempt to discover whether the relationship between Topic Maps and Promise Theory can make configuration knowledge management easier, due to the promise model itself. Topic Maps is an ISO standard for representation and interchange of knowledge. Promise Theory on the other hand is a modelin...

  12. Investigating the effects of organizational culture on brand promise

    OpenAIRE

    Hamed Abbasi; Hamid Reza Abbasi; Ashkan Faraji; Mahsan Hajirasouliha

    2014-01-01

    This paper studies the impacts of four components of organizational culture on brand promise in one of Iranian producer of detergent and sanitary products. The proposed study uses two questionnaires, one for measuring the effects of organizational culture and the other for brand promise in Likert scale. Cronbach alphas for organizational culture and brand promise are calculated as 0.83 and 0.91, respectively. The study has been implemented among 211 regular customers of producer of detergent ...

  13. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    International Nuclear Information System (INIS)

    One-third of breast cancers display amplifications of the ERBB2 gene encoding the HER2 kinase receptor. Trastuzumab, a humanized antibody directed against an epitope on subdomain IV of the extracellular domain of HER2 is used for therapy of HER2-overexpressing mammary tumors. However, many tumors are either natively resistant or acquire resistance against Trastuzumab. Antibodies directed to different epitopes on the extracellular domain of HER2 are promising candidates for replacement or combinatorial therapy. For example, Pertuzumab that binds to subdomain II of HER2 extracellular domain and inhibits receptor dimerization is under clinical trial. Alternative antibodies directed to novel HER2 epitopes may serve as additional tools for breast cancer therapy. Our aim was to generate novel anti-HER2 monoclonal antibodies inhibiting the growth of breast cancer cells, either alone or in combination with tumor necrosis factor-α (TNF-α). Mice were immunized against SK-BR-3 cells and recombinant HER2 extracellular domain protein to produce monoclonal antibodies. Anti-HER2 antibodies were characterized with breast cancer cell lines using immunofluorescence, flow cytometry, immunoprecipitation, western blot techniques. Antibody epitopes were localized using plasmids encoding recombinant HER2 protein variants. Antibodies, either alone or in combination with TNF-α, were tested for their effects on breast cancer cell proliferation. We produced five new anti-HER2 monoclonal antibodies, all directed against conformational epitope or epitopes restricted to the native form of the extracellular domain. When tested alone, some antibodies inhibited modestly but significantly the growth of SK-BR-3, BT-474 and MDA-MB-361 cells displaying ERBB2 amplification. They had no detectable effect on MCF-7 and T47D cells lacking ERBB2 amplification. When tested in combination with TNF-α, antibodies acted synergistically on SK-BR-3 cells, but antagonistically on BT-474 cells. A representative

  14. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Ceran Ceyhan

    2012-10-01

    Full Text Available Abstract Background One-third of breast cancers display amplifications of the ERBB2 gene encoding the HER2 kinase receptor. Trastuzumab, a humanized antibody directed against an epitope on subdomain IV of the extracellular domain of HER2 is used for therapy of HER2-overexpressing mammary tumors. However, many tumors are either natively resistant or acquire resistance against Trastuzumab. Antibodies directed to different epitopes on the extracellular domain of HER2 are promising candidates for replacement or combinatorial therapy. For example, Pertuzumab that binds to subdomain II of HER2 extracellular domain and inhibits receptor dimerization is under clinical trial. Alternative antibodies directed to novel HER2 epitopes may serve as additional tools for breast cancer therapy. Our aim was to generate novel anti-HER2 monoclonal antibodies inhibiting the growth of breast cancer cells, either alone or in combination with tumor necrosis factor-α (TNF-α. Methods Mice were immunized against SK-BR-3 cells and recombinant HER2 extracellular domain protein to produce monoclonal antibodies. Anti-HER2 antibodies were characterized with breast cancer cell lines using immunofluorescence, flow cytometry, immunoprecipitation, western blot techniques. Antibody epitopes were localized using plasmids encoding recombinant HER2 protein variants. Antibodies, either alone or in combination with TNF-α, were tested for their effects on breast cancer cell proliferation. Results We produced five new anti-HER2 monoclonal antibodies, all directed against conformational epitope or epitopes restricted to the native form of the extracellular domain. When tested alone, some antibodies inhibited modestly but significantly the growth of SK-BR-3, BT-474 and MDA-MB-361 cells displaying ERBB2 amplification. They had no detectable effect on MCF-7 and T47D cells lacking ERBB2 amplification. When tested in combination with TNF-α, antibodies acted synergistically on SK-BR-3 cells

  15. Evaluation of N,N-dialkylamides as promising process extractants

    International Nuclear Information System (INIS)

    Studies carried out at BARC, India on the development of new extractants for reprocessing of spent fuel suggested that while straight chain N,N-dihexyloctanamide (DHOA) is promising alternative to TBP for the reprocessing of irradiated uranium based fuels, branched chain N,N-di(2-ethylhexyl)isobutyramide (D2EHIBA) is suitable for the selective recovery of 233U from irradiated Th. In advanced fuel cycle scenarios, the coprocessing of U/Pu stream appears attractive particularly with respect to development of proliferation resistant technologies. DHOA extracted Pu(IV) more efficiently than TBP, both at trace-level concentration as well as under uranium/plutonium loading conditions. Uranium extraction behavior of DHOA was however, similar to that of TBP during the extraction cycle. Stripping behavior of U and Pu (without any reductant) was better for DHOA than that of TBP. It was observed during batch studies that whereas 99% Pu is stripped in four stages in case of DHOA, only 89% Pu is stripped in case of TBP under identical experimental conditions. DHOA offered better fission product decontamination than that of TBP. GANEX (Group ActiNide EXtraction) and ARTIST (Amide-based Radio-resources Treatment with Interim Storage of Transuranics) processes proposed for actinide partitioning use branched chain amides for the selective extraction of uranium from spent fuel feed solutions. The branched-alkyl monoamide (BAMA) proposed to be used in ARTIST process is N,N-di-(2-ethylhexyl)butyramide (D2EHBA). In this context, the extraction behavior of U(VI) and Pu(IV) were compared using D2EHIBA, TBP, and D2EHBA under similar concentration of nitric acid (0.5 - 6M) and of uranium (0-50g/L). These studies suggested that D2EHIBA is a promising extractant for selective extraction of uranium over plutonium in process streams. Similarly, D2EHIBA offered distinctly better decontamination of 233U over Th and fission products under THOREX feed conditions. The possibility of simultaneous

  16. γδ T cell-mediated antibody-dependent cellular cytotoxicity with CD19 antibodies assessed by an impedance-based label-free real-time cytotoxicity assay

    OpenAIRE

    Ursula Jördis Eva Seidel; Fabian eVogt; Ludger eGrosse-Hovest; Gundram eJung; Rupert eHandgretinger; Peter eLang

    2014-01-01

    γδ T cells are not MHC restricted, elicit cytotoxicity against various malignancies, are present in early post-transplant phases in novel stem cell transplantation (SCT) strategies and have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) with monoclonal antibodies (mAbs). These features make γδ T cells promising effector cells for antibody-based immunotherapy in pediatric patients with B-lineage acute lymphoblastic leukemia (ALL). To evaluate combination of human γδ T ce...

  17. γδ T Cell-Mediated Antibody-Dependent Cellular Cytotoxicity with CD19 Antibodies Assessed by an Impedance-Based Label-Free Real-Time Cytotoxicity Assay

    OpenAIRE

    Seidel, Ursula Jördis Eva; Vogt, Fabian; Grosse-Hovest, Ludger; Jung, Gundram; Handgretinger, Rupert; Lang, Peter

    2014-01-01

    γδ T cells are not MHC restricted, elicit cytotoxicity against various malignancies, are present in early post-transplant phases in novel stem cell transplantation strategies and have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) with monoclonal antibodies (mAbs). These features make γδ T cells promising effector cells for antibody-based immunotherapy in pediatric patients with B-lineage acute lymphoblastic leukemia (ALL). To evaluate combination of human γδ T cells wi...

  18. Targeted in vivo inhibition of specific protein-protein interactions using recombinant antibodies.

    Directory of Open Access Journals (Sweden)

    Matej Zábrady

    Full Text Available With the growing availability of genomic sequence information, there is an increasing need for gene function analysis. Antibody-mediated "silencing" represents an intriguing alternative for the precise inhibition of a particular function of biomolecules. Here, we describe a method for selecting recombinant antibodies with a specific purpose in mind, which is to inhibit intrinsic protein-protein interactions in the cytosol of plant cells. Experimental procedures were designed for conveniently evaluating desired properties of recombinant antibodies in consecutive steps. Our selection method was successfully used to develop a recombinant antibody inhibiting the interaction of ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 3 with such of its upstream interaction partners as the receiver domain of CYTOKININ INDEPENDENT HISTIDINE KINASE 1. The specific down-regulation of the cytokinin signaling pathway in vivo demonstrates the validity of our approach. This selection method can serve as a prototype for developing unique recombinant antibodies able to interfere with virtually any biomolecule in the living cell.

  19. Lymphoma, melanoma, colon cancer: diagnosis and treatment with radiolabeled monoclonal antibodies. The 1986 Eugene P. Pendergrass New Horizons Lecture

    International Nuclear Information System (INIS)

    The development of monoclonal antibodies for use as in vivo carriers of radioactivity for diagnosis and therapy of malignant neoplasms is proceeding rapidly within academic and commercial sectors. The author and his colleagues studied anticancer antibodies formed against tumors of both somatic and hematopoietic origins. Several general principles have been established with the work with somatic tumors, including the following: Improved tumor-to-normal-tissue ratios can be achieved with Fab fragments as opposed to whole IgG; each antitumor antibody has a characteristic biodistribution in humans that cannot be readily predicted from tissue or small animal studies; and for many antibodies, there is a strong dependency of tumor uptake on total mass amount of antibody administered (greater uptake with greater mass dose). Initial work with iodine-131 labeled Fab fragments of the antimelanoma antibodies, 96.5 and 48-7, documented that tumor uptake was broadly proportional to antigen content of the tumors and that under optimal conditions, some tumors were sufficiently loaded with radiolabeled antibody to serve as radiation therapy. The antitumor antibody B-72.3, as IgG, has been particularly promising when administered intraperitoneally. In ten patients who were administered I-131 B-72.3 via a Tenkhoff catheter, the sensitivity and specificity of tumor location were excellent for peritoneal implants, and in three of these patients, surgically confirmed tumor was seen with the radiolabeled antibody technique when abdominal computed tomography and magnetic resonance studies were negative

  20. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with {sup 99m}Tc; Estudo de marcacao dos anticorpos monoclonais IOR-CEA-1 e IOR-EGF/R3 com {sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta de Barros Rodrigues

    2005-07-01

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. {sup 99m}Tc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with {sup 99m}Tc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 {mu}L MDP, 3.0 {mu}g Sn{sup 2+}, 1 mL of {sup 99m}Tc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of {sup 99m}Tc was about 2220 MBq (60 mCi). The evidences of the efficiency and

  1. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    better understand the underlying mechanisms of antibody-antigen interaction here we present a pipeline developed by us to structurally classify immunoglobulin antigen binding sites and to infer key sequence residues and other variables that have a prominent role in each structural class....

  2. The self-regulating brain and neurofeedback: Experimental science and clinical promise.

    Science.gov (United States)

    Thibault, Robert T; Lifshitz, Michael; Raz, Amir

    2016-01-01

    Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect. PMID:26706052

  3. Sungkai (Peronema canescens) a promising pioneer tree : an experimental provenance study in Indonesia

    NARCIS (Netherlands)

    Hatta, G.M.

    1999-01-01

    Sungkai ( Peronema canescens Jack.), Verbenaceae, is one among the fancy woods of Indonesia. Sungkai belongs to a small number of species recommended by The Ministry of Forestry for use in the development of industrial forest plantations (IFP). The IFPs are carried out in response to an increasing w

  4. Alternative affinity tools: more attractive than antibodies?

    NARCIS (Netherlands)

    Ruigrok, V.J.B.; Levisson, M.; Eppink, M.H.M.; Smidt, H.; Oost, van der J.

    2011-01-01

    Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids

  5. Detection of Campylobacter species using monoclonal antibodies

    Science.gov (United States)

    Young, Colin R.; Lee, Alice; Stanker, Larry H.

    1999-01-01

    A panel of species specific monoclonal antibodies were raised to Campylobacter coli, Campylobacter jejuni and Campylobacter lari. The isotypes, and cross-reactivity profiles of each monoclonal antibody against an extensive panel of micro- organisms, were determined.

  6. Progranulin antibodies in autoimmune diseases.

    Science.gov (United States)

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

  7. Antibody Production in Plants and Green Algae.

    Science.gov (United States)

    Yusibov, Vidadi; Kushnir, Natasha; Streatfield, Stephen J

    2016-04-29

    Monoclonal antibodies (mAbs) have a wide range of modern applications, including research, diagnostic, therapeutic, and industrial uses. Market demand for mAbs is high and continues to grow. Although mammalian systems, which currently dominate the biomanufacturing industry, produce effective and safe recombinant mAbs, they have a limited manufacturing capacity and high costs. Bacteria, yeast, and insect cell systems are highly scalable and cost effective but vary in their ability to produce appropriate posttranslationally modified mAbs. Plants and green algae are emerging as promising production platforms because of their time and cost efficiencies, scalability, lack of mammalian pathogens, and eukaryotic posttranslational protein modification machinery. So far, plant- and algae-derived mAbs have been produced predominantly as candidate therapeutics for infectious diseases and cancer. These candidates have been extensively evaluated in animal models, and some have shown efficacy in clinical trials. Here, we review ongoing efforts to advance the production of mAbs in plants and algae. PMID:26905655

  8. Occult choriocarcinoma: Detection using radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Occult choriocarcinoma, manifested only by an elevated B-hCG level, can be a difficult management problem. The authors evaluated the ability of I-131-labeled 5F9.3, a murine monoclonal antibody reactive with choriocarcinomas but not hCG, to detect foci of choriocarcinoma in five patients referred with elevated B-hCG levels but in whom the location of residual disease was uncertain. I-131 5F9.3, 0.5-1.0 mCi, was injected intravenously in each patient and images with dynamic background subtraction of TcHSA were obtained at later time points. In four patients chest studies were true positive (confirmed surgically in all), the chest CT scans in these patients had been interpreted as not definitely showing active disease. In the fifth patient no abnormal focus of uptake was seen and subsequent B-hCG levels normalized. In two of the patients with chest lesions, foci of abdominal uptake were seen that were not due to tumor. One of these patients had a partial small bowel obstruction; the other appeared to have a false-positive study. I-131 5F9.3 is a promising agent for the detection of occult choriocarcinomas

  9. Monoclonal Antibodies for Systemic Lupus Erythematosus (SLE

    Directory of Open Access Journals (Sweden)

    Gabriella Moroni

    2010-01-01

    Full Text Available A number of monoclonal antibodies (mAb are now under investigation in clinical trials to assess their potential role in Systemic Lupus Erythematosus (SLE. The most frequently used mAb is rituximab, which is directed against CD20, a membrane protein expressed on B lymphocytes. Uncontrolled trials reported an improvement of SLE activity in non-renal patients and other studies even reported an improvement of severe lupus nephritis unresponsive to conventional treatments. However two randomized trials failed to show the superiority of rituximab over conventional treatment in non renal SLE and in lupus nephritis. Preliminary trials reported promising results with epratuzumab, a humanized mAb directed against CD22, and with belimumab, a human mAb that specifically recognizes and inhibits the biological activity of BLyS a cytokine of the tumornecrosis-factor (TNF ligand superfamily. Other clinical trials with mAb directed against TNF-alpha, interleukin-10 (Il-10, Il-6, CD154, CD40 ligand, IL-18 or complement component C5 are under way. At present, however, in spite of good results reported by some studies, no firm conclusion on the risk-benefit profile of these mAbs in patients with SLE can be drawn from the available studies.

  10. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  11. Virus Strain Discrimination Using Recombinant Antibodies

    OpenAIRE

    Boonham, N.; Barker, I.

    2002-01-01

    Most routine testing for plant viruses is currently carried out using monoclonal and polyclonal antibodies. Traditional methods of antibody production however can be time consuming and require the use of expensive cell culture facilities. Recombinant antibody technology however is starting to make an impact in this area, enabling the selection of antibody fragments in a few weeks compared with the many months associated with traditional methods and requires only basic microbiological faciliti...

  12. Immunoglobulin G4: an odd antibody

    NARCIS (Netherlands)

    R.C. Aalberse; S.O. Stapel; J. Schuurman; T. Rispens

    2009-01-01

    Despite its well-known association with IgE-mediated allergy, IgG4 antibodies still have several poorly understood characteristics. IgG4 is a very dynamic antibody: the antibody is involved in a continuous process of half-molecules (i.e. a heavy and attached light-chain) exchange. This process, also

  13. Development and standardization of multiplexed antibody microarrays for use in quantitative proteomics

    Directory of Open Access Journals (Sweden)

    Sorette M

    2004-12-01

    Full Text Available Abstract Background Quantitative proteomics is an emerging field that encompasses multiplexed measurement of many known proteins in groups of experimental samples in order to identify differences between groups. Antibody arrays are a novel technology that is increasingly being used for quantitative proteomics studies due to highly multiplexed content, scalability, matrix flexibility and economy of sample consumption. Key applications of antibody arrays in quantitative proteomics studies are identification of novel diagnostic assays, biomarker discovery in trials of new drugs, and validation of qualitative proteomics discoveries. These applications require performance benchmarking, standardization and specification. Results Six dual-antibody, sandwich immunoassay arrays that measure 170 serum or plasma proteins were developed and experimental procedures refined in more than thirty quantitative proteomics studies. This report provides detailed information and specification for manufacture, qualification, assay automation, performance, assay validation and data processing for antibody arrays in large scale quantitative proteomics studies. Conclusion The present report describes development of first generation standards for antibody arrays in quantitative proteomics. Specifically, it describes the requirements of a comprehensive validation program to identify and minimize antibody cross reaction under highly multiplexed conditions; provides the rationale for the application of standardized statistical approaches to manage the data output of highly replicated assays; defines design requirements for controls to normalize sample replicate measurements; emphasizes the importance of stringent quality control testing of reagents and antibody microarrays; recommends the use of real-time monitors to evaluate sensitivity, dynamic range and platform precision; and presents survey procedures to reveal the significance of biomarker findings.

  14. Indium antimonide nanowires arrays for promising thermoelectric converters

    Directory of Open Access Journals (Sweden)

    Gorokh G. G.

    2015-02-01

    Full Text Available The authors have theoretically substantiated the possibility to create promising thermoelectric converters based on quantum wires. The calculations have shown that the use of quantum wires with lateral dimensions smaller than quantum confinement values and high concentration and mobility of electrons, can lead to a substantial cooling of one of the contacts up to tens of degrees and to the heating of the other. The technological methods of manufacturing of indium antimonide nanowires arrays with high aspect ratio of the nanowire diameters to their length in the modified nanoporous anodic alumina matrixes were developed and tested. The microstructure and composition of the formed nanostructures were investigated. The electron microscopy allowed establishing that within each pore nanowires are formed with diameters of 35 nm and a length of 35 microns (equal to the matrix thickness. The electron probe x-ray microanalysis has shown that the atomic ratio of indium and antimony in the semiconductor nanostructures amounted to 38,26% and 61,74%, respectively. The current-voltage measurement between the upper and lower contacts of Cu/InSb/Cu structure (1 mm2 has shown that at 2.82 V negative voltage at the emitter contact, current density is 129,8 A/cм2, and the collector contact is heated up to 75 degrees during 150 sec. Thus, the experimental results confirmed the theoretical findings that the quantum wire systems can be used to create thermoelectric devices, which can be widely applied in electronics, in particular, for cooling integrated circuits (processors, thermal controlling of the electrical circuits by changing voltage value.

  15. Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

  16. Passive Immunization against HIV/AIDS by Antibody Gene Transfer

    Directory of Open Access Journals (Sweden)

    Lili Yang

    2014-01-01

    Full Text Available Despite tremendous efforts over the course of many years, the quest for an effective HIV vaccine by the classical method of active immunization remains largely elusive. However, two recent studies in mice and macaques have now demonstrated a new strategy designated as Vectored ImmunoProphylaxis (VIP, which involves passive immunization by viral vector-mediated delivery of genes encoding broadly neutralizing antibodies (bnAbs for in vivo expression. Robust protection against virus infection was observed in preclinical settings when animals were given VIP to express monoclonal neutralizing antibodies. This unorthodox approach raises new promise for combating the ongoing global HIV pandemic. In this article, we survey the status of antibody gene transfer, review the revolutionary progress on isolation of extremely bnAbs, detail VIP experiments against HIV and its related virus conduced in humanized mice and macaque monkeys, and discuss the pros and cons of VIP and its opportunities and challenges towards clinical applications to control HIV/AIDS endemics.

  17. Dynamic force spectroscopy of parallel individual mucin1-antibody bonds

    Energy Technology Data Exchange (ETDEWEB)

    Sulchek, T A; Friddle, R W; Langry, K; Lau, E; Albrecht, H; Ratto, T; DeNardo, S; Colvin, M E; Noy, A

    2005-05-02

    We used atomic force microscopy (AFM) to measure the binding forces between Mucin1 (MUC1) peptide and a single chain antibody fragment (scFv) selected from a scFv library screened against MUC1. This binding interaction is central to the design of the molecules for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from non-specific interactions by tethering the antibody and MUC1 molecules to the AFM tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the bond rupture events corresponding to different number of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for mono-, bi-, and tri-valent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for mono and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.

  18. Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

    OpenAIRE

    Baker, J. R.; Lukes, Y G; Burman, K. D.

    1984-01-01

    Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimul...

  19. Adsorption orientations and immunological recognition of antibodies on graphene

    Science.gov (United States)

    Vilhena, J. G.; Dumitru, A. C.; Herruzo, Elena T.; Mendieta-Moreno, Jesús I.; Garcia, Ricardo; Serena, P. A.; Pérez, Rubén

    2016-07-01

    MD results and the AFM images demonstrate that the IgG antibodies are strongly adsorbed, do not unfold, and retain their secondary and tertiary structures upon deposition. Statistical analysis of the AFM images shows that many of the antibodies adopt vertical orientations, even at very small coverages, which expose at least one Fab binding site for recognition events. Single molecule force spectroscopy experiments demonstrate the immunological response of the deposited antibodies by recognizing its specific antigens. The above properties together with the strong anchoring and preservation of the secondary structure, make graphene an excellent candidate for the development of immunosensors. Electronic supplementary information (ESI) available: Further details concerning the experimental methods, the MD simulation protocols, and the characterization and stability of the different adsorption configurations. See DOI: 10.1039/C5NR07612A

  20. Labeling and use of monoclonal antibodies in immunofluorescence: protocols for cytoskeletal and nuclear antigens.

    Science.gov (United States)

    Bauer, Christoph R

    2014-01-01

    monoclonal antibodies for two key targets within a cell, namely, (a) the cytoskeleton with emphasis on microtubules (Cramer and Mitchison, J Cell Biol 31:179-189, 1995; Traub et al., Biol Cell 90:319-337, 1998; Desai et al., Methods Cell Biol 61:385-412, 1999) and (b) the nuclear pore complex (Davis and Blobel, Cell 45:699-709, 1986; Kimura et al., Mol Cell Biol 23:1304-1315, 2003). The two protocols which differ substantially in using either a chemical fixation/permeabilization approach versus a one-step coagulation protocol are chosen to offer the reader tools to design their own procedures and adapt them accordingly to fit their individual experimental setup and the biological question asked. PMID:24515489

  1. Solid phase double-antibody radioimmunoassay procedure

    International Nuclear Information System (INIS)

    The present invention is concerned with the radioimmunoassay (RIA) procedure for assaying body fluid content of an antigenic substance which may either be an antigen itself or a hapten capable of being converted, such as by means of reaction with a protein, to an antigenic material. The present invention is concerned with a novel and improved modification of a double-antibody RIA technique in which there is a first antibody that is specific to the antigenic substance suspected to be present in a body fluid from which the assay is intended. The second antibody, however, is not specific to the antigenic substance or analyte, but is an antibody against the first antibody

  2. Production of Monoclonal Antibody against Human Nestin.

    Science.gov (United States)

    Hadavi, Reza; Zarnani, Amir Hassan; Ahmadvand, Negah; Mahmoudi, Ahmad Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Sadeghi, Mohammad-Reza; Soltanghoraee, Haleh; Akhondi, Mohammad Mehdi; Tarahomi, Majid; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah

    2010-04-01

    We have employed a peptide-based antibody generation protocol for producing antibody against human nestin. Using a 12-mer synthetic peptide from repetitive region of human nestin protein devoid of any N- or O-glyco-sylation sequences, we generated a mouse monoclonal antibody capable of recognizing human, mouse, bovine, and rat nestin. A wide variety of nestin proteins ranging from 140-250 kDa was detected by this antibody. This antibody is highly specific and functional in applications such as ELISA, flow cytometry, immunocytochemistry, and Western blot assays. PMID:23407796

  3. Production of Monoclonal Antibody against Human Nestin

    OpenAIRE

    Hadavi, Reza; Zarnani, Amir Hassan; Ahmadvand, Negah; Mahmoudi, Ahmad Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Sadeghi, Mohammad-Reza; Soltanghoraee, Haleh; Akhondi, Mohammad mehdi; Tarahomi, Majid; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah

    2010-01-01

    We have employed a peptide-based antibody generation protocol for producing antibody against human nestin. Using a 12-mer synthetic peptide from repetitive region of human nestin protein devoid of any N- or O-glyco-sylation sequences, we generated a mouse monoclonal antibody capable of recognizing human, mouse, bovine, and rat nestin. A wide variety of nestin proteins ranging from 140–250 kDa was detected by this antibody. This antibody is highly specific and functional in applications such a...

  4. The Use of Monoclonal Antibodies in Human Prion Disease

    Science.gov (United States)

    Bodemer, Walter

    Detection of PrP and its pathological isoform(s) is the key to understanding the etiology and pathogenesis of transmissible spongiform encephalopathy. There is ample evidence that PrP isoforms constitute a major component of an unknown and perhaps unconventional infectious agent. An etiological relationship between human and zoonotic transmissible spongiform encephalopathies may be revealed with monoclonal antibodies. Knowledge of the conformational transition rendering a nonpathogenic, almost ubiquitous cellular protein into a pathogenic one is crucial to defining pathomechanisms. The stepwise or even continuous formation of pathogenic molecules can be monitored. Any improvement in the early diagnosis could help to conceive new therapeutic measures which are not currently available. Determination of PrP isoforms in tissue, cells, or body fluids may be of prognostic value. Many experimental approaches in molecular medicine and molecular biology of the prion protein already rely on monoclonal antibodies. Recombinant antibodies such as the single-chain Fv may soon replace traditional hybridoma techniques. Binding affinity can easily be manipulated by a number of techniques, including in vitro mutagenesis - a step which could never be carried out using the traditional hybridoma technology. Monoclonal antibodies are and will remain an essential support for ongoing research on the prion protein in general and on the unconventional infectious prions.

  5. Vaccination, squalene and anti-squalene antibodies: facts or fiction?

    Science.gov (United States)

    Lippi, Giuseppe; Targher, Giovanni; Franchini, Massimo

    2010-04-01

    Squalene, a hydrocarbon obtained for commercial purposes primarily from shark liver oil and other botanic sources, is increasingly used as an immunologic adjuvant in several vaccines, including seasonal and the novel influenza A (H1N1) 2009 pandemic flu vaccines. Nearly a decade ago, squalene was supposed to be the experimental anthrax vaccine ingredient that caused the onset of Persian Gulf War syndrome in many veterans, since antibodies to squalene were detected in the blood of most patients affected by this syndrome. This evidence has raised a widespread concern about the safety of squalene containing adjuvants (especially MF59) of influenza vaccines. Nevertheless, further clinical evidence clearly suggested that squalene is poorly immunogenic, that low titres of antibodies to squalene can be also detected in sera from healthy individuals, and that neither the presence of anti-squalene antibodies nor their titre is significantly increased by immunization with vaccines containing squalene (or MF59) as an adjuvant. This review summarizes the current scientific evidence about the relationship between squalene, anti-squalene antibodies and vaccination. PMID:20206873

  6. 9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Erysipelothrix Rhusiopathiae Antibody... REQUIREMENTS Antibody Products § 113.452 Erysipelothrix Rhusiopathiae Antibody. Erysipelothrix Rhusiopathiae Antibody is a specific antibody product containing antibodies directed against one or more somatic...

  7. Monoclonal Antibody Therapies against Anthrax

    OpenAIRE

    Zhaochun Chen; Mahtab Moayeri; Robert Purcell

    2011-01-01

    Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. It not only causes natural infection in humans but also poses a great threat as an emerging bioterror agent. The lethality of anthrax is primarily attributed to the two major virulence factors: toxins and capsule. An extensive effort has been made to generate therapeutically useful monoclonal antibodies to each of the virulence components: protective antigen (PA), lethal factor (LF) and ede...

  8. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  9. Epigenetics of the antibody response

    OpenAIRE

    Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

    2013-01-01

    Epigenetic marks, such as DNA methylation, histone posttranslational modifications and microRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR) and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and microRNAs modulate t...

  10. Pharmacological selection of antibodies for immunoscintigraphy

    International Nuclear Information System (INIS)

    The recent development of hybridoma technology has resulted in the production of monoclonal antibodies that recognize a variety of tumor antigens. Many antibodies have been developed and some of them are used with different success in clinical practice. A list of criteria is proposed for the selection of antibodies suitable for imaging studies illustrated with the example of two monoclonal antibodies anti-CEA and 19.9 used in colorectal carcinoma imaging. Monoclonal antibodies obtained today are not truly tumor-specific, they are tumor-associated; this suggests that some cross-reactions with normal tissues exist. For immunoscintigraphical use it is important to select antibodies which procedure high tumor cell staining with limited reactivity against normal tissues. Antibodies can be separated into F(ab')2 and Fab fragments which diffuse more easily into the tumor with a rapid clearance from the circulation giving higher tumor to normal tissues ratio at an early time. Antibodies with both high affinity and avidity towards tumor cell receptors produce better imaging results. Antibodies can be labelled directly with iodine or technetium and with indium using chelating agents. In vivo kinetics of radiolabelled antibodies are very different considering the nuclide and the labelling method used. Pharmacokinetics on nude mice grated with human tumors are very useful for selecting the most appropriate nuclide antibody fragment and the most efficient labelling technique for a given application. (author)

  11. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer.

    Science.gov (United States)

    Welz, Christian; Emmert, Steffen; Canis, Martin; Becker, Sven; Baumeister, Philipp; Shimizu, Tetsuji; Morfill, Gregor E; Harréus, Uli; Zimmermann, Julia L

    2015-01-01

    Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment. PMID:26588072

  12. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer.

    Directory of Open Access Journals (Sweden)

    Christian Welz

    Full Text Available Head and neck squamous cell cancer (HNSCC is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s. IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.

  13. Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets?

    Science.gov (United States)

    Moreth, Jens; Mavoungou, Chrystelle; Schindowski, Katharina

    2013-01-01

    Alzheimer's disease (AD) is the most common dementia in the industrialized world, with prevalence rates well over 30% in the over 80-years-old population. The dementia causes enormous costs to the social healthcare systems, as well as personal tragedies for the patients, families and caregivers. AD is strongly associated with Amyloid-beta (Aβ) protein aggregation, which results in extracellular plaques in the brain, and according to the amyloid cascade hypothesis appeared to be a promising target for the development of AD therapeutics. Within the past decade convincing data has arisen positioning the soluble prefibrillar Aβ-aggregates as the prime toxic agents in AD. However, different Aβ aggregate species are described but their remarkable metastability hampers the identification of a target species for immunization. Passive immunotherapy with monoclonal antibodies (mAbs) against Aβ is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function. Preliminary data from off-label treatment of a small cohort for 3 years with intravenous polyclonal immunoglobulins (IVIG) that appear to target different conformational epitopes indicate a cognitive stabilization. Thus, it might be the more promising strategy reducing the whole spectrum of Aβ-aggregates than to focus on a single aggregate species for immunization. PMID:23663286

  14. Cold Atmospheric Plasma: A Promising Complementary Therapy for Squamous Head and Neck Cancer

    Science.gov (United States)

    Welz, Christian; Emmert, Steffen; Canis, Martin; Becker, Sven; Baumeister, Philipp; Shimizu, Tetsuji; Morfill, Gregor E.; Harréus, Uli; Zimmermann, Julia L.

    2015-01-01

    Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment. PMID:26588072

  15. Development of antibody against sulfamethazine

    International Nuclear Information System (INIS)

    Sulfamethazine (SMT) is widely used to treat bacterial and protozoan infections in food animals. So its residue has been detected in various food products, and in Europe, the tolerance level for sulfonamides in meat and milk is 100 ng/g. To ensure that residues in animal food products do not exceed this limit, a simple, sensitive, and rapid method to determinate their residues in animal tissues is needed. In this paper the development of polyclonal or monoclonal antibodies against sulfamethazine (SMT) and a simplified method to identify residual sulfamethazine by radio immunoassay (RIA) is presented. Polyclonal antibodies (PcAbs) against sulfamethazine (SMT) were obtained by immunizing rabbits with SMT-conjugated bovine serum albumin (BSA). The association constants (Ka) of the PcAbs were higher than 108 and the cross-reactivities with Sulfadiazine(SD), Sulfaquinoxaline(SQX) which were structurally related compounds were lower than 0.05%(RIA). Simultaneous, six strains of hybridoma cell were prepared which can secrete monoclonal antibodies (McAbs) against SMT . The Ka of the McAbs against SMT were higher than 107 and the cross-reactivities with SD, SQX were lower than 0.1%(RIA). (authors)

  16. Monoclonal antibodies in targeted therapy

    Directory of Open Access Journals (Sweden)

    Beata Powroźnik

    2012-09-01

    Full Text Available Targeted therapy is a new therapeutic method consisting in the inhibition of specific molecular pathways. In modern therapy, the key role is played by monoclonal antibodies, included in the group of biological agents. The success of molecularly targeted therapy is to define the proper “molecular target”, selecting the right drug active against a specific “target” and selecting a group of patients who benefit from treatment. Introduction of targeted therapy resulted in improved results of the treatment of many serious and chronic diseases. In general, targeted molecular therapies have good toxicity profiles, but some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. Patient selection and proper monitoring significantly decrease the risk of life-threatening adverse events. Data concerning late side effects are still unavailable because of the short follow-up of molecularly targeted therapy. Currently in the U.S. and Europe there are approximately 31 registered therapeutic monoclonal antibodies, while 160 are subjected to clinical trials. This paper presents an overview of therapeutic monoclonal antibodies currently used in therapy and the present state of knowledge about them. 

  17. Generation and characterization of chicken egg yolk antibodies (IgY) against TNFR1.

    Science.gov (United States)

    Hashemi, M; Amirijavid, S; Entezari, M; Shafaroodi, H; Saghafi, Z Jokar

    2015-01-01

    TNF is from a big family of cytokines with different activities in different parts of the body. Among the various activities of TNFR1, induction of apoptosis by a receptor appears to be an attractive and promising one. This can be achieved through the death domain of the receptor in cells that are stimulated by ligand, to induce apoptosis. Activation of the receptor occurs through its occupation by ligands or its antagonists such as antibodies. Several kinds of antibodies, including antibodies of mammals and birds are used in the research and therapy field. Avian antibodies are highly regarded which is due to the many positive characteristics they have. Firstly, total protein of TNFR1 was cloned. Blood sampling was performed, white blood cell separation, extraction of RNA and at cDNA synthesis. After making sure from synthesis of cDNA, it was used as template for PCR reaction. The cloned fragment in the prokaryotic expression vector, pET28a, transferred to prokaryotic host, BL21(DE3) and the protein (TNFR1) expressed. After protein purification by affinity column were injected to immunize the chickens. Interestingly, antibodies purified from egg yolk of immunized chickens, in ELISA assay showed sufficient specificity. Such antibodies could able to ensure quick and immediate protection against several biotargets (Fig. 4, Ref. 37). PMID:25924641

  18. Advances in monoclonal antibody application in myocarditis

    Institute of Scientific and Technical Information of China (English)

    Li-na HAN; Shuang HE; Yu-tang WANG; Li-ming YANG; Si-yu LIU; Ting ZHANG

    2013-01-01

    Monoclonal antibodies have become a part of daily preparation technologies in many laboratories.Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases,inflammatory diseases,cancer,and other immune-associated diseases.This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis,an inflammatory disease of the heart,could be a novel approach in the future.In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis,we,through a significant amount of literature research both domestic and abroad,developed a systematic elaboration of monoclonal antibodies,pathogenesis of myocarditis,and application of monoclonal antibodies in myocarditis.This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future.Under conventional therapy,myocarditis is typically associated with congestive heart failure as a progressive outcome,indicating the need for alternative therapeutic strategies to improve long-term results.Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis,we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above.However,several issues remain.The technology on howto make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues.If we are to further stimulate

  19. New high affinity monoclonal antibodies recognize non-overlapping epitopes on mesothelin for monitoring and treating mesothelioma.

    Science.gov (United States)

    Zhang, Yi-Fan; Phung, Yen; Gao, Wei; Kawa, Seiji; Hassan, Raffit; Pastan, Ira; Ho, Mitchell

    2015-01-01

    Mesothelin is an emerging cell surface target in mesothelioma and other solid tumors. Most antibody drug candidates recognize highly immunogenic Region I (296-390) on mesothelin. Here, we report a group of high-affinity non-Region I rabbit monoclonal antibodies. These antibodies do not compete for mesothelin binding with the immunotoxin SS1P that binds Region I of mesothelin. One pair of antibodies (YP218 and YP223) is suitable to detect soluble mesothelin in a sandwich ELISA with high sensitivity. The new assay can also be used to measure serum mesothelin concentration in mesothelioma patients, indicating its potential use for monitoring patients treated with current antibody therapies targeting Region I. The antibodies are highly specific and sensitive in immunostaining of mesothelioma. To explore their use in tumor therapy, we have generated the immunotoxins based on the Fv of these antibodies. One immunotoxin (YP218 Fv-PE38) exhibits potent anti-tumor cytotoxicity towards primary mesothelioma cell lines in vitro and an NCI-H226 xenograft tumor in mice. Furthermore, we have engineered a humanized YP218 Fv that retains full binding affinity for mesothelin-expressing cancer cells. In conclusion, with their unique binding properties, these antibodies may be promising candidates for monitoring and treating mesothelioma and other mesothelin-expressing cancers. PMID:25996440

  20. Binding hot-spots in an antibody-ssDNA interface: a molecular dynamics study.

    Science.gov (United States)

    Wang, Yeng-Tseng; Lee, Wen-Jay

    2012-10-30

    Simulating antigen-antibody interactions is essential for elucidating antigen-antibody mechanics. Proteins interactions are vital for elucidating antibody-ssDNA associations in immunology. Therefore, this study investigated the dissociation of the human systemic lupus erythematosus antibody-ssDNA complex structure. Dissociation (i.e. the distance between the center of mass of the ssDNA and the antibody) is also studied using the potential of mean force calculations based on molecular dynamics and the explicit water model. The MM-PBSA method is also used to prove our dissociation simulations. With 605 nanosecond molecular dynamics simulations, the results indicate that the 8 residues (i.e. Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2)), and the five inter-protein molecular hydrogen bonds may profoundly impact the antibody-ssDNA interaction, a finding which may be useful for protein engineering of this antibody-ssDNA structure. Experimental binding affinity of this antibody-ssDNA complex equals 7.00 kcal mol(-1). Our dissociation binding affinity is 7.96 ± 0.33 kcal mol(-1) and MM-PBSA binding affinity is 9.12 ± 1.65 kcal mol(-1), which is close to the experimental value. Additionally, the 8 residues Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2) may play a more significant role in developing bioactive antibody analogues. PMID:23079742

  1. Antibody-guided irradiation of hepatic metastases using intrahepatically administered radiolabelled anti-CEA antibodies with simultaneous and reversible hepatic blood flow stasis using biodegradable starch microspheres.

    Science.gov (United States)

    Epenetos, A A; Courtenay-Luck, N; Dhokia, B; Snook, D; Hooker, G; Lavender, J P; Hemmingway, A; Carr, D; Paraharalambous, M; Bosslet, K

    1987-12-01

    Two monoclonal antibodies to carcinoembryonic antigen (CEA) were radiolabelled with 131I and used for the treatment of hepatic metastases in a patient who had a primary colonic carcinoma. Approximately 100 mCi of 131I-labelled antibody were administered via the hepatic artery on two occasions. On the second occasion, radiolabelled antibody was given concurrently with biodegradable starch microspheres in an attempt to enhance tumour uptake of antibody by achieving temporary stasis or delay of hepatic blood flow. The procedure was carried out uneventfully. There was clinical improvement and a fall in circulating CEA levels after each course of treatment. Furthermore, after the second course of therapy the clinical improvement was sustained for a longer period (more than 3 months) and there was evidence of diminution in the size of some of the liver metastases. Regional administration of 131I-labelled anti-CEA antibody concurrently with biodegradable starch microspheres appears to be a promising new method for the treatment of hepatic metastases from colonic carcinoma. PMID:3449789

  2. Study Hints At HPV Vaccine's Cancer Prevention Promise

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159696.html Study Hints at HPV Vaccine's Cancer Prevention Promise Fewer ... that can lead to cervical cancer, a new study shows. Canadian researchers found that young women who ...

  3. Salivary Gland Biopsy Shows Promise to Helping to Diagnose Parkinson's

    Science.gov (United States)

    ... Parkinson's HelpLine Learn More Science News Salivary Gland Biopsy Shows Promise to Helping to Diagnose Parkinson’s - Mar ... team performed a procedure called a needle core biopsy of the submandibular glands in 15 people who ...

  4. Promise Zone Round 2 Applicant Geography and Goal Data

    Data.gov (United States)

    Department of Housing and Urban Development — This dataset includes Promise Zone initiative round II applicant project data from 111 urban, rural, and tribal communities who consented to share their application...

  5. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    Science.gov (United States)

    ... 1999 Spotlight on Research 2014 February 2014 (historical) Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder Replacing a protein that is crucial to ensuring that the skin’s ...

  6. Doctors Often Overestimate Promise of Newly Approved Drugs

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158267.html Doctors Often Overestimate Promise of Newly Approved Drugs Many ... and Drug Administration's expedited approval process could mislead doctors about the new drugs' actual benefits, researchers warn. ...

  7. Gene Therapy Shows Early Promise Against Heart Failure

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158046.html Gene Therapy Shows Early Promise Against Heart Failure Inserting ... who suffer from heart failure: A trial using gene therapy appears to have boosted patients' cardiac function. " ...

  8. Modeling bispecific monoclonal antibody interaction with two cell membrane targets indicates the importance of surface diffusion.

    Science.gov (United States)

    Sengers, Bram G; McGinty, Sean; Nouri, Fatma Z; Argungu, Maryam; Hawkins, Emma; Hadji, Aymen; Weber, Andrew; Taylor, Adam; Sepp, Armin

    2016-07-01

    We have developed a mathematical framework for describing a bispecific monoclonal antibody interaction with two independent membrane-bound targets that are expressed on the same cell surface. The bispecific antibody in solution binds either of the two targets first, and then cross-links with the second one while on the cell surface, subject to rate-limiting lateral diffusion step within the lifetime of the monovalently engaged antibody-antigen complex. At experimental densities, only a small fraction of the free targets is expected to lie within the reach of the antibody binding sites at any time. Using ordinary differential equation and Monte Carlo simulation-based models, we validated this approach against an independently published anti-CD4/CD70 DuetMab experimental data set. As a result of dimensional reduction, the cell surface reaction is expected to be so rapid that, in agreement with the experimental data, no monovalently bound bispecific antibody binary complexes accumulate until cross-linking is complete. The dissociation of the bispecific antibody from the ternary cross-linked complex is expected to be significantly slower than that from either of the monovalently bound variants. We estimate that the effective affinity of the bivalently bound bispecific antibody is enhanced for about 4 orders of magnitude over that of the monovalently bound species. This avidity enhancement allows for the highly specific binding of anti-CD4/CD70 DuetMab to the cells that are positive for both target antigens over those that express only one or the other We suggest that the lateral diffusion of target antigens in the cell membrane also plays a key role in the avidity effect of natural antibodies and other bivalent ligands in their interactions with their respective cell surface receptors. PMID:27097222

  9. Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination.

    Science.gov (United States)

    Ramanathan, Sudarshini; Dale, Russell C; Brilot, Fabienne

    2016-04-01

    Myelin oligodendrocyte glycoprotein (MOG) is a protein exclusively expressed on the surface of oligodendrocytes and myelin in the central nervous system. MOG has been identified as a putative candidate autoantigen and autoantibody target in demyelination for almost three decades, with extensive literature validating its role in murine models of experimental autoimmune encephalomyelitis. Seminal studies using murine anti-MOG antibodies have highlighted the fact that antibodies that target epitopes of native MOG in its conformational state, rather than linearized or denature`d MOG, are biologically relevant. However, the relevance of anti-MOG antibodies in humans has been difficult to decipher over the years due to varying methods of detection as well as the fact that it was assumed that these antibodies would be clinically associated with multiple sclerosis. There is now international consensus that anti-MOG antibodies are important in both pediatric and adult demyelination, and the clinical association of MOG antibody-associated demyelination has been refined to include acute disseminated encephalomyelitis, relapsing and bilateral optic neuritis, and transverse myelitis. Anti-MOG antibodies are now thought not to be associated with multiple sclerosis in adults. Patients with MOG antibody-associated demyelination appear to have a unique clinical, radiological, and therapeutic profile, which represents a major advance in their diagnosis and management. It is imperative to understand whether anti-MOG antibodies are indeed pathogenic, and if so, their mechanisms of action. As it has become apparent that there are differences in MOG epitope binding between species, translation of animal studies to human demyelination should be analyzed in this context. Further work is required to identify the specific epitope binding sites in human disease and pathogenic mechanisms of anti-MOG antibodies, as well optimal therapeutic strategies to improve prognosis and minimize

  10. A second look at enrollment changes after the Kalamazoo Promise

    OpenAIRE

    Hershbein, Brad J.

    2013-01-01

    While previous research has documented how the Kalamazoo Promise, the most prominent and generous place-based college scholarship program, increased enrollment in Kalamazoo Public Schools, this paper qualifies and quantifies the characteristics of students who were induced to enter - or stay - in the district. In particular, it analyzes the origins and destinations, socioeconomic composition, and school-level sorting behavior associated with student flows around the time of the Promise announ...

  11. OptMAVEn--a new framework for the de novo design of antibody variable region models targeting specific antigen epitopes.

    Directory of Open Access Journals (Sweden)

    Tong Li

    Full Text Available Antibody-based therapeutics provides novel and efficacious treatments for a number of diseases. Traditional experimental approaches for designing therapeutic antibodies rely on raising antibodies against a target antigen in an immunized animal or directed evolution of antibodies with low affinity for the desired antigen. However, these methods remain time consuming, cannot target a specific epitope and do not lead to broad design principles informing other studies. Computational design methods can overcome some of these limitations by using biophysics models to rationally select antibody parts that maximize affinity for a target antigen epitope. This has been addressed to some extend by OptCDR for the design of complementary determining regions. Here, we extend this earlier contribution by addressing the de novo design of a model of the entire antibody variable region against a given antigen epitope while safeguarding for immunogenicity (Optimal Method for Antibody Variable region Engineering, OptMAVEn. OptMAVEn simulates in silico the in vivo steps of antibody generation and evolution, and is capable of capturing the critical structural features responsible for affinity maturation of antibodies. In addition, a humanization procedure was developed and incorporated into OptMAVEn to minimize the potential immunogenicity of the designed antibody models. As case studies, OptMAVEn was applied to design models of neutralizing antibodies targeting influenza hemagglutinin and HIV gp120. For both HA and gp120, novel computational antibody models with numerous interactions with their target epitopes were generated. The observed rates of mutations and types of amino acid changes during in silico affinity maturation are consistent with what has been observed during in vivo affinity maturation. The results demonstrate that OptMAVEn can efficiently generate diverse computational antibody models with both optimized binding affinity to antigens and reduced

  12. Serrumab: a human monoclonal antibody that counters the biochemical and immunological effects of Tityus serrulatus venom.

    Science.gov (United States)

    Pucca, Manuela Berto; Zoccal, Karina Furlan; Roncolato, Eduardo Crosara; Bertolini, Thaís Barboza; Campos, Lucas Benício; Cologna, Camila Takeno; Faccioli, Lúcia Helena; Arantes, Eliane Candiani; Barbosa, José Elpidio

    2012-01-01

    In Brazil, the species Tityus serrulatus is responsible for the most severe cases of scorpion envenomation. There is currently a need for new scorpion anti-venoms that are more effective and less harmful. This study attempted to produce human monoclonal antibodies capable of inhibiting the activity of T. serrulatus venom (TsV), using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Four rounds of phage antibody selection were performed, and the round with the highest phage antibody titer was chosen for the production of monoclonal phage antibodies and for further analysis. The scFv 2A, designated serrumab, was selected for the production and purification of soluble antibody fragments. In a murine peritoneal macrophage cell line (J774.1), in vitro assays of the cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were performed. In male BALB/c mice, in vivo assays of plasma urea, creatinine, aspartate transaminase, and glucose were performed, as well as of neutrophil recruitment and leukocyte counts. It was found that serrumab inhibited the TsV-induced increases in the production of IL-6, TNFα, and IL-10 in J774.1 cells. The in vivo inhibition assay showed that serrumab also prevented TsV-induced increases in the plasma levels of urea, creatinine, aspartate transaminase, and glucose, as well as preventing the TsV-induced increase in neutrophil recruitment. The results indicate that the human monoclonal antibody serrumab is a candidate for inclusion in a mixture of specific antibodies to the various toxins present in TsV. Therefore, serrumab shows promise for use in the production of new anti-venom. PMID:22424317

  13. HIV aspartyl protease inhibitors as promising compounds against Candida albicans

    Institute of Scientific and Technical Information of China (English)

    André; Luis; Souza; dos; Santos

    2010-01-01

    Cells of Candida albicans(C.albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated my coses of almost all inner organs,especially in immunocompromised patients.In this context,both the host immune status and the ability of C.albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance;in this last case,culminating in the establishment of successful infection knownas candidiasis.C.albicans possesses a potent arma-mentarium consisting of several virulence moleculesthat help the fungal cells to escape of the host immuneresponses.There is no doubt that the secretion of aspartyl-type proteases,designated as Saps,are one of the major virulence attributes produced by C.albicans cells,since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions.For these reasons,Saps clearly hold promise as new potential drug targets.Corroborating this hypothesis,the introduction of new anti-human immunodeficiency virus drugs of the as party l protease inhibitor-type(HIV PIs) have emerged as new agents for the inhibition of Saps.The introduction of HIV PIs has revolutionized the treatment of HIV disease,reducing opportunistic infections,especially candidiasis.The attenuation of candidal infections in HIV-infected individuals might not solely have resulted from improved immunological status,but also as a result of direct inhibition of C.albicans Saps.In this article,we review updates on the beneficial effects of HIV PIs against the human fungal pathogen C.albicans,focusing on the effects of these compounds on Sap activity,growth behavior,morphological architecture,cellular differentiation,fungal adhesion to animal cells and abiotic materials,modulation of virulence factors,experimental candidiasis infection,and their synergistic actions with classical antifungal agents.

  14. Production of biological reagents for radioimmunoassay second antibody

    International Nuclear Information System (INIS)

    The experimental production of second antibody to be used in hormonal assays, in which the first antibody is raised in rabbits, is described. Four sheep were immunized with the rabbit immunoglobulin prepared at IPEN-CNEN laboratory. Their antisera were evaluated by the human thyrotropin radioimmunoassay employing materials provided by the National Hormone and Pituitary Program (USA), in comparison with a reference antiserum of known quality, produced in goat by the Radioassay Systems Laboratories - RSL (USA). From the fourth booster injection the animals developed antiserum with titer similar to that exhibited by the commercial product, even presenting higher values. These antisera are now being examinated for the optimal conditions of precipitation before be packed for future use and distribution. (author)

  15. Power laws and extreme values in antibody repertoires

    Science.gov (United States)

    Boyer, Sebastien; Biswas, Dipanwita; Scaramozzino, Natale; Kumar, Ananda Soshee; Nizak, Clément; Rivoire, Olivier

    2015-03-01

    Evolution by natural selection involves the succession of three steps: mutations, selection and proliferation. We are interested in describing and characterizing the result of selection over a population of many variants. After selection, this population will be dominated by the few best variants, with highest propensity to be selected, or highest ``selectivity.'' We ask the following question: how is the selectivity of the best variants distributed in the population? Extreme value theory, which characterizes the extreme tail of probability distributions in terms of a few universality class, has been proposed to describe it. To test this proposition and identify the relevant universality class, we performed quantitative in vitro experimental selections of libraries of >105 antibodies using the technique of phage display. Data obtained by high-throughput sequencing allows us to fit the selectivity distribution over more than two decades. In most experiments, the results show a striking power law for the selectivity distribution of the top antibodies, consistent with extreme value theory.

  16. Monoclonal antibody therapy in multiple myeloma: where do we stand and where are we going?

    Science.gov (United States)

    Thanendrarajan, Sharmilan; Davies, Faith E; Morgan, Gareth J; Schinke, Carolina; Mathur, Pankaj; Heuck, Christoph J; Zangari, Maurizio; Epstein, Joshua; Yaccoby, Shmuel; Weinhold, Niels; Barlogie, Bart; van Rhee, Frits

    2016-01-01

    Multiple myeloma is a plasma cell malignancy that is characterized by refractory and relapsing course of disease. Despite the introduction of high-dose chemotherapy in combination with autologous stem cell transplantation and innovative agents such as proteasome inhibitors and immunomodulatory drugs, achieving cure in multiple myeloma is a challenging endeavor. In the last couple of years, enormous advances were made in implementing monoclonal antibody therapy in multiple myeloma. A large number of preclinical and clinical studies have been introduced successfully, demonstrating a safe and efficient administration of monoclonal antibodies in multiple myeloma. In particular, the application of monoclonal antibodies in combination with immunomodulatory drugs, proteasome inhibitors, corticosteroids or conventional chemotherapy seem to be promising and will expand the treatment arsenal for patients with multiple myeloma. PMID:26888183

  17. Affitins as alternative to antibodies

    International Nuclear Information System (INIS)

    Full text of publication follows. We have developed the use of Sac7d archaeal polypeptide and its homologues as a non-antibody scaffold from which artificial affinity proteins (Affitins) can be derived with a number of favorable properties. Affitins show affinity (sub-nanomolar) and specificity that compare well with those of antibodies [Ref.1]. They are thermally (up to 90 C. degrees) and chemically stable (pH 0-12+, denaturants), well expressed in E. coli (up to 200 mg/L), lack disulfide bridge and have a size compatible with chemical synthesis (7 kDa). We have demonstrated their use as reagents for intra-cellular inhibition [Ref.1], affinity purification [Ref.2], immuno-localization [Ref.3], protein chip array [Ref.4] and biosensors [Ref.5]. We have also shown that Affitins are plastic enough to tolerate several mutagenesis schemes while their fold and their favorable properties are conserved [Ref.6]. Compared to Affitins, monoclonal antibodies are 20 times larger, less stable and more complex molecules. Furthermore, the remarkable stability properties of Affitins make them suited for demanding labeling protocols that are usually used for peptides. All together, these results show that Affitins should be well suited for biomedical applications where fine tuning of the affinity reagent properties is needed. References: [Ref.1] Mouratou, B. et al., (2007), Proc Natl Acad Sci U S A 104, 17983-17988; [Ref.2] Krehenbrink, M. et al. (2008), J Mol Biol 383, 1058-1068; [Ref.3] Buddelmeijer, N. et al. (2009), J Bacteriol 191, 161-168; [Ref.4] Cinier, M. et al. (2009), Bioconjug. Chem. 20, 2270-2277; [Ref.5] Miranda, F. F. et al. (2011), Biosens. Bioelectron. 26, 4184-4190; [Ref.6] Behar G.et al. (2013), Protein Eng Des Sel. 26(4):267-75. (authors)

  18. Protective antiviral antibodies that lack neutralizing activity: precedents and evolution of concepts.

    Science.gov (United States)

    Schmaljohn, Alan L

    2013-07-01

    Antibody-mediated resistance to viral disease is often attributed solely to neutralizing antibodies (NAbs) despite a body of evidence -- more than 30 years in the making -- to show that other populations of antibodies (protective non-neutralizing antibodies, PnNAbs) can also contribute and are sometimes pivotal in host resistance to viruses. Recently, interest in varieties of PnNAbs has been restored and elevated by an HIV vaccine trial in which virus-specific nNAbs have been highlighted as a positive correlate of immunity. Here, I briefly review some of the historical precedents with many viruses other than HIV, along with the emergence of data over the course of some four decades, pointing emphatically to the importance of subsets of antiviral antibodies that operate by mechanisms other than classical virus neutralization. Foremost among suspected mechanisms of protection by PnNAbs is antibody-dependent cellular cytotoxicty (ADCC), but additional mechanisms have sometimes been incriminated or not experimentally excluded. Examples are given for the diversity of proteins and cognate epitopes bound by PnNAbs. Some such epitopes are restricted to virus-infected cell surfaces or found on secreted proteins; others may be associated with virions but unavailable to antibodies during much of the viral cycle; these are epitopes variously described as cryptic, transitional, dynamic, or reversibly masked. PMID:24191933

  19. Use of Solid Phase Second Antibody for the Radioimmunoassay of T3

    International Nuclear Information System (INIS)

    Solid phase second antibody separation techniques includes the reaction between antigen and the first antibody takes place in the liquid phase after which the bounded antigen fraction is separated by the addition of a second antibody immobilised on a solid support. In the present study purified goat anti rabbit gamma globulin was immobilised on magnetised polyacrolein particles. The titre of the product was determined followed by assay design to optimise reagent volumes and incubation time. Experimental results showed that a design using 50μl of standard T solution, 50 μl of 125I-labeled T3, 50 μl of T3 antibody solution, first incubation time of 2 hours at 37oC and the addition of 50 μl of second antibody magnetic particles suspension followed by a second incubation for 1 hour yielded sufficient sensitivity and satisfactory results in the working area of interest. Assay performance was tested by comparing the characteristic parameter values with those of the control, i.e. commercial RIA-T3 kits from BATAN/Amersham and the double antibody separation method described previously. Stability testing of the second antibody magnetic particles was determined by evaluation of the maximum and nonspecific binding values over time, the suspension of magnetised particles was shown to be sufficiently stable for at least 3 months when stored at 4oC. (author). 3 tabs., 4 figs

  20. Avian influenza in ovo vaccination with replication defective recombinant adenovirus in chickens: vaccine potency, antibody persistence, and maternal antibody transfer.

    Science.gov (United States)

    Mesonero, Alexander; Suarez, David L; van Santen, Edzard; Tang, De-Chu C; Toro, Haroldo

    2011-06-01

    levels throughout the experimental period (34 wk of age). AdTW68.H5(ch)-immunized breeder hens effectively transferred MtAb to progeny chickens. The level of MtAb in the progenies was consistent with the levels detected in the breeders, i.e., intramuscularly boosted breeders transferred higher concentrations of antibodies to the offspring. Maternal antibodies declined with time in the progenies and achieved marginal levels by 34 days of age. Chickens with high maternal antibody levels that were vaccinated either in ovo or via mucosal routes (ocular or spray) did not seroconvert. In contrast, chickens without MtAb successfully developed specific antibody levels after either in ovo or mucosal vaccination. These results indicate that high levels of MtAb interfered with active Ad-vectored vaccination. PMID:21793447

  1. Mathematical analysis of equilibrium on 2-site immunoradiometric assay using anti-human TSH monoclonal antibody

    International Nuclear Information System (INIS)

    A mathematical analysis of equilibrium was adapted on a practical 2-site immunoradiometric assay (IRMA) using 10 minune monoclonal antibodies (Mabs) to human TSH. The affinity constant of 10 Mabs was from 2.5 x 108 to 3.3 x 1010 M-1. The dose-response curves using appropriate combinations of Mab-coated bead and 125I-labeled Mab were compared with the theoretical curves calculated from mathematical analysis of quilibrium. Theoretical curves were directly affected by the affinity constants in which antibodies with higher affinity constants showed higher binding activity of tracer. However, the curves which antibodies have more than 1 x 109 M-1 and 1 x 1010 M-1 for capture antibody and tracer antibody did not show remarkable change, but were similar with the curve obtained from unlimited affinity constant. From these curves, the maximum and minimum detectable doses were approx. 2 x 10-10 M and 4 x 10-14 M, respectively. Seven out of 10 experimental curves for TSH showed good consistency with the corresponding theoretical curves which indicated that a mathematical analysis of equilibrium was useful to presume experimental results using monoclonal antibody. (author)

  2. Nucleic acid aptamers: clinical applications and promising new horizons

    OpenAIRE

    Ni, Xiaohua; Castanares, Mark; Mukherjee, Amarnath; Shawn E Lupold

    2011-01-01

    Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic. Since the discovery of aptamers in the early 1990s, great efforts have been made to ma...

  3. A bivalent virus-like particle based vaccine induces a balanced antibody response against both enterovirus 71 and norovirus in mice.

    Science.gov (United States)

    Wang, Xiaoli; Ku, Zhiqiang; Dai, Wenlong; Chen, Tan; Ye, Xiaohua; Zhang, Chao; Zhang, Yingyi; Liu, Qingwei; Jin, Xia; Huang, Zhong

    2015-10-26

    Noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. Genogroup II.4 (GII.4) strains are responsible for the majority of norovirus outbreaks. Enterovirus 71 (EV71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in Asia-Pacific regions, resulting in significant morbidity and mortality in young children. However, no vaccine is commercially available for either norovirus GII.4 or EV71. Recombinant virus-like particles (VLPs) derived from either GII.4 or EV71 have been shown to be promising monovalent vaccine candidates. In this study, we investigate the possibility to formulate a VLP-based bivalent vaccine for both norovirus GII.4 and EV71. The GII.4- and EV71-VLPs were produced in a baculovirus-insect cell expression system. A bivalent combination vaccine comprised of GII.4 and EV71 VLPs was formulated and compared with monovalent GII.4- and EV71-VLPs for their immunogenicity in mice. We found that the bivalent vaccine elicited durable antibody responses toward both GII.4 and EV71, and the antibody titers were comparable to that induced by the monovalent vaccines, indicating there is no immunological interference between the two antigens in the combination vaccine. More significantly, the bivalent vaccine-immunized mouse sera could efficiently neutralize EV71 infection and block GII.4-VLP binding to mucin. Together, our results demonstrate that the experimental combination vaccine comprised of GII.4 and EV71-VLPs is able to induce a balanced protective antibody response, and therefore strongly support further preclinical and clinical development of such a bivalent VLP vaccine targeting both norovirus GII.4 and EV71. PMID:26424606

  4. Further evaluation of an ELISA kit for detection of antibodies to a nonstructural protein of foot-and-mouth disease virus.

    Science.gov (United States)

    Fukai, Katsuhiko; Nishi, Tatsuya; Morioka, Kazuki; Yamada, Manabu; Yoshida, Kazuo; Kitano, Rie; Yamazoe, Reiko; Kanno, Toru

    2016-04-01

    An ELISA kit for detection of antibodies to a nonstructural protein of foot-and-mouth disease (FMDV) was further evaluated using sequentially collected serum samples of experimentally infected animals, because the sensitivity of the kit used in a previous study was significantly low in field animals. The kit fully detected antibodies in infected animals without vaccination; however, the first detections of antibodies by the kit were later than those by the liquid-phase blocking ELISA that is used for serological surveillance in the aftermath of outbreaks in Japan, for detection of antibodies to structural proteins of FMDV. Additionally, although the kit effectively detected antibodies in infected cattle with vaccination, there were several infected pigs with vaccination for which the kit did not detect antibodies during the experimental period. Taken together, the kit may not be suitable for serological surveillance after an FMD outbreak either with or without emergency vaccination in FMD-free countries. PMID:26498533

  5. Immunogenicity of an engineered internal image antibody.

    OpenAIRE

    Billetta, R; Hollingdale, M. R.; Zanetti, M

    1991-01-01

    We engineered an antibody expressing in the third complementarity-determining region of its heavy chain variable region a "foreign" epitope, the repetitive tetrapeptide Asn-Ala-Asn-Pro (NANP) of the circumsporozoite protein of Plasmodium falciparum parasite, one of the etiologic agents of malaria in humans. A monoclonal antibody to P. falciparum specific for the (NANP)n amino acid sequence bound to the engineered antibody, and a synthetic (NANP)3 peptide blocked this interaction. Immunization...

  6. A general approach to antibody thermostabilization

    OpenAIRE

    McConnell, Audrey D; Xue ZHANG; Macomber, John L.; Chau, Betty; Sheffer, Joseph C; Rahmanian, Sorena; Hare, Eric; Spasojevic, Vladimir; Horlick, Robert A.; King, David J; Bowers, Peter M.

    2014-01-01

    Antibody engineering to enhance thermostability may enable further application and ease of use of antibodies across a number of different areas. A modified human IgG framework has been developed through a combination of engineering approaches, which can be used to stabilize antibodies of diverse specificity. This is achieved through a combination of complementarity-determining region (CDR)-grafting onto the stable framework, mammalian cell display and in vitro somatic hypermutation (SHM). Thi...

  7. Antibody-Mediated Lung Transplant Rejection

    OpenAIRE

    Hachem, Ramsey

    2012-01-01

    Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunctio...

  8. Imaging tumors with radiolabelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Using a metallic radionuclide, either directly bound to a monoclonal antibody, or to a chelating agent (such as di-ethylenetriamine-pentaacetic acid (DTPA)) conjugated to the antibody, a tumor can be traced rapidly and with high specificity. The labelled antibody is injected into the host. In some cases, a localization of distant metastases is possible, giving an indication of tumor spreading. Detection occurs by photoscanning. (Auth.)

  9. Haptens, conjugates and antibodies for pyrimethanil fungicide

    OpenAIRE

    Mercader Badia, Josep Vicent; Abad Fuentes, Antonio; Abad Somovilla, Antonio; Agulló, Consuelo

    2012-01-01

    [EN] The invention relates to haptens, conjugates and antibodies for pyrimethanil fungicide. In addition, the invention relates to the use of pyrimethanil conjugates as assay antigens or immunogens in order to obtain antibodies of the aforementioned fungicide, and to the use of the labelled derivatives of pyrimethanil as assay antigens. The invention also relates to a pyrimethanil analysis method using the antibodies obtained, at times together with assay antigens which are conjugates or labe...

  10. Oncology monoclonal antibodies expenditure trends and reimbursement projections in the emerging Balkan market

    OpenAIRE

    Jakovljevic, Mihajlo B.

    2014-01-01

    Monoclonal antibodies applied in clinical oncology present a therapeutic promise for many patients with cancer. Nevertheless these expensive protocols are associated with extremely high acquisition and administration costs. The issue of societal affordability of such treatment options is particularly at stake among middle income European economies. Medicines Agency of Serbia issues regular annual reports on public expenditure on pharmaceuticals since 2004. According to these official data tot...

  11. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K;

    2012-01-01

    microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment......The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody...

  12. Antibody-coated protein A-bearing Staphylococcus aureus: a versatile and stable immune reagent

    International Nuclear Information System (INIS)

    The human β2-microglobulin antigen-antibody system was used as a model to illustrate the versatility of a microradioimmunoassay technique using protein A-bearing Staphylococcus aureus Cowan I strain (SACI) bacteria as a non-specific immunoadsorbent in place of a second antibody. Experimental conditions are described for a sensitive microassay which makes it possible to process large numbers of samples more rapidly and with minimum handling. Furthermore, SACI coated with specific antibodies by mixing with unfractionated antisera are a versatile reagent not only for radioimmunoassays but also for use as molecular probes to characterize cell surface antigens. Antibody-coated SACI could be lyophilized and proved extremely stable in storage thus providing a unique advantage for use in binding inhibition assays and as versatile reagent for clinical and investigative immunology. (Auth.)

  13. A sensitive radioimmunoassay for the determination of antibodies to mouse hepatitis virus

    International Nuclear Information System (INIS)

    A solid-phase radioimmunoassay is described for the detection of antibodies to mouse hepatitis virus. Viruses were purified by velocity and isopycnic gradient centrifugation and 96-well plastic plates were coated with viral antigens. To allow the detection of most serotypes of low titered antisera, a pool of antigens from several viral serotypes were employed. The second antibody, an affinity-purified goat antimouse immunoglobulin, detects IgG, IgM and IgA antibodies. This assay is more sensitive than either the plaque reduction assay or the commercially available enzyme-linked immunosorbant assay and proved to be useful for screening mouse colonies for the presence of mouse hepatitis virus, following seroconversion in experimental animals and in the production of monoclonal antibodies to both structural and nonstructural proteins. (Auth.)

  14. Monoclonal antibodies as diagnostics; an appraisal

    Directory of Open Access Journals (Sweden)

    Siddiqui M

    2010-01-01

    Full Text Available Ever since the development of Hybridoma Technology in 1975 by Kohler and Milstein, our vision for antibodies as tools for research for prevention, detection and treatment of diseases, vaccine production, antigenic characterization of pathogens and in the study of genetic regulation of immune responses and disease susceptibility has been revolutionized. The monoclonal antibodies being directed against single epitopes are homogeneous, highly specific and can be produced in unlimited quantities. In animal disease diagnosis, they are very useful for identification and antigenic characterization of pathogens. Monoclonal antibodies have tremendous applications in the field of diagnostics, therapeutics and targeted drug delivery systems, not only for infectious diseases caused by bacteria, viruses and protozoa but also for cancer, metabolic and hormonal disorders. They are also used in the diagnosis of lymphoid and myeloid malignancies, tissue typing, enzyme linked immunosorbent assay, radio immunoassay, serotyping of microorganisms, immunological intervention with passive antibody, antiidiotype inhibition, or magic bullet therapy with cytotoxic agents coupled with anti mouse specific antibody. Recombinant deoxyribonucleic acid technology through genetic engineering has successfully led to the possibility of reconstruction of monoclonal antibodies viz. chimeric antibodies, humanized antibodies and complementarily determining region grafted antibodies and their enormous therapeutic use.

  15. Mouse monoclonal antibodies against estrogen receptor.

    Science.gov (United States)

    De Rosa, Caterina; Rossi, Valentina; Abbondanza, Ciro

    2014-01-01

    The production of monoclonal antibodies, by cloning hybridoma derived from the fusion of myeloma cells and spleen lymphocytes, has allowed to obtain great advances in many fields of biological knowledge. The use of specific antibodies to the estrogen receptor, in fact, has been an invaluable method to bring out its mechanisms of action and its effects, both genomic and extra-genomic. Here we describe, step by step, the production of monoclonal antibodies, starting from protocol for antigen preparation to the selection of antibody-secreting hybridoma. PMID:25182770

  16. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Thrombocytopenia Platelet Factor 4 Antibody Related tests: Complete Blood Count , Platelet Count , Serotonin Release Assay, Heparin-induced Platelet Aggregation All content on Lab Tests Online has been ...

  17. Monoclonal Antibodies for Lipid Management.

    Science.gov (United States)

    Feinstein, Matthew J; Lloyd-Jones, Donald M

    2016-07-01

    In recent years, biochemical and genetic studies have identified proprotein convertase subtilisin/kexin type 9 (PCSK9) as a major mediator of low-density lipoprotein cholesterol (LDL-c) levels and thereby a potential novel target for reducing risk of coronary heart disease (CHD). These observations led to the development of PCSK9 inhibitors, which lower LDL-c levels more than any other non-invasive lipid-lowering therapy presently available. The PCSK9 inhibitors furthest along in clinical trials are subcutaneously injected monoclonal antibodies. These PCSK9 inhibitors have demonstrated LDL-c-lowering efficacy with acceptable safety in phase III clinical trials and may offer a useful therapy in addition to maximally tolerated HMG-CoA reductase inhibitors (statins) in certain patient groups. Longer-term data are required to ensure sustained efficacy and safety of this new class of medications. This review provides an overview of the biology, genetics, development, and clinical trials of monoclonal antibodies designed to inhibit PCSK9. PMID:27221501

  18. Antiphospholipid Antibodies and Systemic Scleroderma

    Directory of Open Access Journals (Sweden)

    Awa Oumar Touré

    2013-03-01

    Full Text Available Objective: Antiphospholipid antibodies (APLs could be associated with an increased risk of vascular pathologies in systemic scleroderma. The aim of our study was to search for APLs in patients affected by systemic scleroderma and to evaluate their involvement in the clinical manifestations of this disease. Materials and Methods: We conducted a cross-sectional descriptive study, from January 2009 until August 2010, with patients received at the Department of Dermatology (Dakar, Senegal. Blood samples were taken at the hematology laboratory and were analyzed for the presence of APLs. Results: Forty patients were recruited. Various types of either isolated or associated APLs were found in 23 patients, i.e. 57.5% of the study population. The most frequently encountered antibody was IgG anti-β2 GPI (37.5% of the patients, followed by anticardiolipins (17.5% and lupus anticoagulants (5%. No statistically significant association of positive antiphospholipid-related tests to any of the scleroderma complications could be demonstrated. Conclusion: A high proportion of patients showing association of systemic scleroderma and APLs suggests the presence of a morbid correlation between these 2 pathologies. It would be useful to follow a cohort of patients affected by systemic scleroderma in order to monitor vascular complications following confirmation of the presence of antiphospholipid syndrome.

  19. Algae as protein factories: expression of a human antibody and the respective antigen in the diatom Phaeodactylum tricornutum.

    Directory of Open Access Journals (Sweden)

    Franziska Hempel

    Full Text Available Microalgae are thought to offer great potential as expression system for various industrial, therapeutic and diagnostic recombinant proteins as they combine high growth rates with all benefits of eukaryotic expression systems. Moreover, microalgae exhibit a phototrophic lifestyle like land plants, hence protein expression is fuelled by photosynthesis, which is CO(2-neutral and involves only low production costs. So far, however, research on algal bioreactors for recombinant protein expression is very rare calling for further investigations in this highly promising field. In this study, we present data on the expression of a monoclonal human IgG antibody against the Hepatitis B surface protein and the respective antigen in the diatom Phaeodactylum tricornutum. Antibodies are fully-assembled and functional and accumulate to 8.7% of total soluble protein, which complies with 21 mg antibody per gram algal dry weight. The Hepatitis B surface protein is functional as well and is recognized by algae-produced and commercial antibodies.

  20. Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

    DEFF Research Database (Denmark)

    Da Roit, F.; Engelberts, P. J.; Taylor, R. P.;

    2015-01-01

    The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-delta inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated...... the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies....... Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of...

  1. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik

    2010-01-01

    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do not...... scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  2. Stratification of Antibody-Positive Subjects by Antibody Level Reveals an Impact of Immunogenicity on Pharmacokinetics

    OpenAIRE

    Zhou, Lei; Hoofring, Sarah A.; Wu, Yu; Vu, Thuy; Ma, Peiming; Swanson, Steven J.; Chirmule, Narendra; Starcevic, Marta

    2012-01-01

    The availability of highly sensitive immunoassays enables the detection of antidrug antibody (ADA) responses of various concentrations and affinities. The analysis of the impact of antibody status on drug pharmacokinetics (PK) is confounded by the presence of low-affinity or low-concentration antibody responses within the dataset. In a phase 2 clinical trial, a large proportion of subjects (45%) developed ADA following weekly dosing with AMG 317, a fully human monoclonal antibody therapeutic....

  3. High level transient production of recombinant antibodies and antibody fusion proteins in HEK293 cells

    OpenAIRE

    Jäger, Volker; Büssow, Konrad; Wagner, Andreas; Weber, Susanne; Hust, Michael; Frenzel, André; Schirrmann, Thomas

    2013-01-01

    Background The demand of monospecific high affinity binding reagents, particularly monoclonal antibodies, has been steadily increasing over the last years. Enhanced throughput of antibody generation has been addressed by optimizing in vitro selection using phage display which moved the major bottleneck to the production and purification of recombinant antibodies in an end-user friendly format. Single chain (sc)Fv antibody fragments require additional tags for detection and are not as suitable...

  4. Antibodies to human fetal erythroid cells from a nonimmune phage antibody library

    OpenAIRE

    Huie, Michael A.; Cheung, Mei-Chi; Muench, Marcus O.; Becerril, Baltazar; Kan, Yuet W.; Marks, James D.

    2001-01-01

    The ability to isolate fetal nucleated red blood cells (NRBCs) from the maternal circulation makes possible prenatal genetic analysis without the need for diagnostic procedures that are invasive for the fetus. Such isolation requires antibodies specific to fetal NRBCs. To generate a panel of antibodies to antigens present on fetal NRBCs, a new type of nonimmune phage antibody library was generated in which multiple copies of antibody fragments are displayed on each pha...

  5. Copenhagen's climate finance promise: six key questions

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, J. Timmons [Brown University (United States); Stadelmann, Martin [University of Zurich (Switzerland); Huq, Saleemul

    2010-02-15

    One clear promise emerged from the confusion of the 2009 climate talks in Copenhagen. This was to provide short- and long-term 'climate finance' to help developing countries – especially the most vulnerable – adapt to climate impacts. The promise seemed simple enough: wealthier nations would pledge US$10 billion a year from 2010-2012, ramping up to US$100 billion a year starting in 2020. This was also touted as a way to help developing countries avoid high-carbon pathways of development by adopting lower-emitting power sources such as solar or natural gas. But a closer look at the Copenhagen promise unearths at least six big questions – any one of which could seriously challenge the trust these funds were designed to build.

  6. Congestion Service Facilities Location Problem with Promise of Response Time

    Directory of Open Access Journals (Sweden)

    Dandan Hu

    2013-01-01

    Full Text Available In many services, promise of specific response time is advertised as a commitment by the service providers for the customer satisfaction. Congestion on service facilities could delay the delivery of the services and hurts the overall satisfaction. In this paper, congestion service facilities location problem with promise of response time is studied, and a mixed integer nonlinear programming model is presented with budget constrained. The facilities are modeled as M/M/c queues. The decision variables of the model are the locations of the service facilities and the number of servers at each facility. The objective function is to maximize the demands served within specific response time promised by the service provider. To solve this problem, we propose an algorithm that combines greedy and genetic algorithms. In order to verify the proposed algorithm, a lot of computational experiments are tested. And the results demonstrate that response time has a significant impact on location decision.

  7. Local and Global Trust Based on the Concept of Promises

    CERN Document Server

    Bergstra, Jan

    2009-01-01

    We use the notion of a promise to define local trust between agents possessing autonomous decision-making. An agent is trustworthy if it is expected that it will keep a promise. This definition satisfies most commonplace meanings of trust. Reputation is then an estimation of this expectation value that is passed on from agent to agent. Our definition distinguishes types of trust, for different behaviours, and decouples the concept of agent reliability from the behaviour on which the judgement is based. We show, however, that trust is fundamentally heuristic, as it provides insufficient information for agents to make a rational judgement. A global trustworthiness, or community trust can be defined by a proportional, self-consistent voting process, as a weighted eigenvector-centrality function of the promise theoretical graph.

  8. Promise-based management: the essence of execution.

    Science.gov (United States)

    Sull, Donald N; Spinosa, Charles

    2007-04-01

    Critical initiatives stall for a variety of reasons--employee disengagement, a lack of coordination between functions, complex organizational structures that obscure accountability, and so on. To overcome such obstacles, managers must fundamentally rethink how work gets done. Most of the challenges stem from broken or poorly crafted commitments. That's because every company is, at its heart, a dynamic network of promises made between employees and colleagues, customers, outsourcing partners, or other stakeholders. Executives can overcome many problems in the short-term and foster productive, reliable workforces for the long-term by practicing what the authors call "promise-based management," which involves cultivating and coordinating commitments in a systematic way. Good promises share five qualities: They are public, active, voluntary, explicit, and mission based. To develop and execute an effective promise, the "provider" and the "customer" in the deal should go through three phases of conversation. The first, achieving a meeting of minds, entails exploring the fundamental questions of coordinated effort: What do you mean? Do you understand what I mean? What should I do? What will you do? Who else should we talk to? In the next phase, making it happen, the provider executes on the promise. In the final phase, closing the loop, the customer publicly declares that the provider has either delivered the goods or failed to do so. Leaders must weave and manage their webs of promises with great care-encouraging iterative conversation and making sure commitments are fulfilled reliably. If they do, they can enhance coordination and cooperation among colleagues, build the organizational agility required to seize new business opportunities, and tap employees' entrepreneurial energies. PMID:17432155

  9. Passive antibody transfer in chickens to model maternal antibody after avian influenza vaccination

    Science.gov (United States)

    Birds transfer maternal antibodies (MAb) to their offspring through the egg yolk where the antibody is absorbed and enters the circulatory system. These maternal antibodies, depending on the pathogen, can provide early protection from some diseases, but it may also interfere with the vaccination re...

  10. Promising design options for the encapsulated nuclear heat source reactor

    International Nuclear Information System (INIS)

    Promising design options for the Encapsulated Nuclear Heat Source (ENHS) liquid-metal cooled fast reactor were identified during the first year of the DOE NERI program sponsored feasibility study. Many opportunities for incorporation of innovations in design and fabrication were identified. Three of the innovations are hereby described: a novel IHX (intermediate heat exchanger) made of a relatively small number of rectangular channels, an ENHS module design featuring 100% natural circulation, and a novel conceptual design of core support and fuelling. As a result of the first year study the ENHS concept appears more practical and more promising than perceived at the outset of this study. (authors)

  11. Cuban Monoclonal Antibodies for Radioimmunodiagnosis and Radioimmunotherapy of Cancer Diseases

    International Nuclear Information System (INIS)

    The Centre of Molecular Immunology produces monoclonal antibodies for treating cancer diseases. We are mainly focus on two target systems; one is the epidermal growth factor receptor (EGF-R) because there is a tremendous relationship between the EGF/EGF-R system and several human tumours such as lung, head and neck, ovarian breast and brain cancers; the second one is the ganglioside system, the relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues. Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) that was obtained by complementarity-determining regions grafting of a murine mAb (ior egf/r3) to a human framework having remarkable antiproliferative, pro-apoptotic, and antiangiogenic effects. A Phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary (intracerebral) administration of a single dose of nimotuzumab (h-R3) labelled with increasing doses of 188Re. All patients bearing astrocytomas grade III/IV should be treated previously with conventional therapies and have an EGF-R overexpression in the tumour, demonstrated by immunohistochemical study. Maximal tolerated dose was 3 mg of the h-R3 labelled with 10 mCi of 188Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast and colon

  12. Systemically Administered IgG Anti-Toxin Antibodies Protect the Colonic Mucosa during Infection with Clostridium difficile in the Piglet Model

    OpenAIRE

    Cohen, Ocean R.; Steele, Jennifer A.; Zhang, Quanshun; Schmidt, Diane J.; Wang, Yuankai; Hamel, Philip E. S.; Beamer, Gillian; Xu, Bingling; Tzipori, Saul

    2014-01-01

    The use of anti-toxin human monoclonal antibodies (HMab) as treatment for C. difficile infection has been investigated in animal models and human clinical trials as an alternative to or in combination with traditional antibiotic therapy. While HMab therapy appears to be a promising option, how systemically administered IgG antibodies protect the colonic mucosa during Clostridium difficile infection is unknown. Using the gnotobiotic piglet model of Clostridium difficile infection, we administe...

  13. 21 CFR 866.3290 - Gonococcal antibody test (GAT).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gonococcal antibody test (GAT). 866.3290 Section... antibody test (GAT). (a) Identification. A gonococcal antibody test (GAT) is an in vitro device that..., indirect fluorescent antibody, or radioimmunoassay, antibodies to Neisseria gonorrhoeae in sera...

  14. TSOL18 Vaccine Antigen of Taenia solium: Development of Monoclonal Antibodies and Field Testing of the Vaccine in Cameroon

    Directory of Open Access Journals (Sweden)

    Assana, E.

    2010-01-01

    Full Text Available Chapter 1 reviews the literature about the immunological aspects of taeniid cestode infections and the existing vaccines against Taenia solium cysticercosis in pigs. One of the most promising vaccines is TSOL18, a protein that has been identified in the oncosphere of Taenia solium and expressed as a recombinant molecule in E. coli. Repeated experimental trials have shown that this vaccine is able to protect up to 100% of the immunised pigs against a challenge infection with T. solium. Antibodies raised by the vaccine are capable of killing the parasite in in vitro cultures and it is believed that antibody and complement mediated killing of invading parasites is the major protective immune mechanism induced by vaccination with TSOL18. The identification of the villages with a high risk of T. solium infection, which could subsequently be used in the vaccine trial, is reported in chapter 2. A survey was conducted in 150 households owning 1756 pigs in the rural areas of Mayo-Danay division in the far north region of Cameroon. A questionnaire survey was carried out to collect information on the pig farming system and to identify potential risk factors for T. solium cysticercosis infection in pigs. Blood samples were collected from 398 pigs with the aim of estimating the sero-prevalence of Taenia solium cysticercosis. The results showed that 90.7% of the pigs were free roaming during the dry season and that 42.7% of households keeping pigs in the rural areas had no latrine facility. Seventy six percent of the interviewed pig owners affirmed that the members of the household used open field defecation. ELISA for antigen and antibody detection showed an apparent prevalence of porcine cysticercosis of 24.6% and 32.2%, respectively. A Bayesian approach using the conditional dependence between the two diagnostic tests indicated that the true sero-prevalence of cysticercosis in Mayo-Danay was 26.6%. Binary logistic regression analysis indicated that the

  15. Evaluation of Ion Mobility-Mass Spectrometry for Comparative Analysis of Monoclonal Antibodies

    Science.gov (United States)

    Ferguson, Carly N.; Gucinski-Ruth, Ashley C.

    2016-05-01

    Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics.

  16. Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier.

    Science.gov (United States)

    Couch, Jessica A; Yu, Y Joy; Zhang, Yin; Tarrant, Jacqueline M; Fuji, Reina N; Meilandt, William J; Solanoy, Hilda; Tong, Raymond K; Hoyte, Kwame; Luk, Wilman; Lu, Yanmei; Gadkar, Kapil; Prabhu, Saileta; Ordonia, Benjamin A; Nguyen, Quyen; Lin, Yuwen; Lin, Zhonghua; Balazs, Mercedesz; Scearce-Levie, Kimberly; Ernst, James A; Dennis, Mark S; Watts, Ryan J

    2013-05-01

    Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting antibody uptake in brain. Nevertheless, there are limited data on the therapeutic properties including safety liabilities that will enable successful development of TfR-based therapeutics. We evaluate TfR/BACE1 bispecific antibody variants in mouse and show that reducing TfR binding affinity improves not only brain uptake but also peripheral exposure and the safety profile of these antibodies. We identify and seek to address liabilities of targeting TfR with antibodies, namely, acute clinical signs and decreased circulating reticulocytes observed after dosing. By eliminating Fc effector function, we ameliorated the acute clinical signs and partially rescued a reduction in reticulocytes. Furthermore, we show that complement mediates a residual decrease in reticulocytes observed after Fc effector function is eliminated. These data raise important safety concerns and potential mitigation strategies for the development of TfR-based therapies that are designed to cross the blood-brain barrier. PMID:23636093

  17. Evaluation of Ion Mobility-Mass Spectrometry for Comparative Analysis of Monoclonal Antibodies.

    Science.gov (United States)

    Ferguson, Carly N; Gucinski-Ruth, Ashley C

    2016-05-01

    Analytical techniques capable of detecting changes in structure are necessary to monitor the quality of monoclonal antibody drug products. Ion mobility mass spectrometry offers an advanced mode of characterization of protein higher order structure. In this work, we evaluated the reproducibility of ion mobility mass spectrometry measurements and mobiligrams, as well as the suitability of this approach to differentiate between and/or characterize different monoclonal antibody drug products. Four mobiligram-derived metrics were identified to be reproducible across a multi-day window of analysis. These metrics were further applied to comparative studies of monoclonal antibody drug products representing different IgG subclasses, manufacturers, and lots. These comparisons resulted in some differences, based on the four metrics derived from ion mobility mass spectrometry mobiligrams. The use of collision-induced unfolding resulted in more observed differences. Use of summed charge state datasets and the analysis of metrics beyond drift time allowed for a more comprehensive comparative study between different monoclonal antibody drug products. Ion mobility mass spectrometry enabled detection of differences between monoclonal antibodies with the same target protein but different production techniques, as well as products with different targets. These differences were not always detectable by traditional collision cross section studies. Ion mobility mass spectrometry, and the added separation capability of collision-induced unfolding, was highly reproducible and remains a promising technique for advanced analytical characterization of protein therapeutics. Graphical Abstract ᅟ. PMID:26988372

  18. Promising applications of graphene and graphene-based nanostructures

    Science.gov (United States)

    Nguyen, Bich Ha; Hieu Nguyen, Van

    2016-06-01

    The present article is a review of research works on promising applications of graphene and graphene-based nanostructures. It contains five main scientific subjects. The first one is the research on graphene-based transparent and flexible conductive films for displays and electrodes: efficient method ensuring uniform and controllable deposition of reduced graphene oxide thin films over large areas, large-scale pattern growth of graphene films for stretchble transparent electrodes, utilization of graphene-based transparent conducting films and graphene oxide-based ones in many photonic and optoelectronic devices and equipments such as the window electrodes of inorganic, organic and dye-sensitized solar cells, organic light-emitting diodes, light-emitting electrochemical cells, touch screens, flexible smart windows, graphene-based saturated absorbers in laser cavities for ultrafast generations, graphene-based flexible, transparent heaters in automobile defogging/deicing systems, heatable smart windows, graphene electrodes for high-performance organic field-effect transistors, flexible and transparent acoustic actuators and nanogenerators etc. The second scientific subject is the research on conductive inks for printed electronics to revolutionize the electronic industry by producing cost-effective electronic circuits and sensors in very large quantities: preparing high mobility printable semiconductors, low sintering temperature conducting inks, graphene-based ink by liquid phase exfoliation of graphite in organic solutions, and developing inkjet printing technique for mass production of high-quality graphene patterns with high resolution and for fabricating a variety of good-performance electronic devices, including transparent conductors, embedded resistors, thin-film transistors and micro supercapacitors. The third scientific subject is the research on graphene-based separation membranes: molecular dynamics simulation study on the mechanisms of the transport of

  19. Promising applications of graphene and graphene-based nanostructures

    Science.gov (United States)

    Nguyen, Bich Ha; Hieu Nguyen, Van

    2016-06-01

    The present article is a review of research works on promising applications of graphene and graphene-based nanostructures. It contains five main scientific subjects. The first one is the research on graphene-based transparent and flexible conductive films for displays and electrodes: efficient method ensuring uniform and controllable deposition of reduced graphene oxide thin films over large areas, large-scale pattern growth of graphene films for stretchble transparent electrodes, utilization of graphene-based transparent conducting films and graphene oxide-based ones in many photonic and optoelectronic devices and equipments such as the window electrodes of inorganic, organic and dye-sensitized solar cells, organic light-emitting diodes, light-emitting electrochemical cells, touch screens, flexible smart windows, graphene-based saturated absorbers in laser cavities for ultrafast generations, graphene-based flexible, transparent heaters in automobile defogging/deicing systems, heatable smart windows, graphene electrodes for high-performance organic field-effect transistors, flexible and transparent acoustic actuators and nanogenerators etc. The second scientific subject is the research on conductive inks for printed electronics to revolutionize the electronic industry by producing cost-effective electronic circuits and sensors in very large quantities: preparing high mobility printable semiconductors, low sintering temperature conducting inks, graphene-based ink by liquid phase exfoliation of graphite in organic solutions, and developing inkjet printing technique for mass production of high-quality graphene patterns with high resolution and for fabricating a variety of good-performance electronic devices, including transparent conductors, embedded resistors, thin-film transistors and micro supercapacitors. The third scientific subject is the research on graphene-based separation membranes: molecular dynamics simulation study on the mechanisms of the transport of

  20. Severe alcoholic hepatitis: Glucocorticoid saves lives and transplantation is promising

    Institute of Scientific and Technical Information of China (English)

    Alain Braillon

    2011-01-01

    Glucocorticosteroids have been used as the only treatment for a long time which significantly reduced the mortality of the patients with severe alcoholic hepatitis. The efficacy of transplantation has been recently addressed in a pilot study. The result seems promising but needs larger multicenter trials.

  1. Differentiation therapy:a promising strategy forcancer treatment

    Institute of Scientific and Technical Information of China (English)

    MinYan; QuentinLiu

    2016-01-01

    Poor differentiation is an important hallmark of cancer cells, and differentiation therapy holds great promise for cancer treatment. The restoration of IkB kinase α (IKKα) leads to the differentiation of nasopharyngeal carcinoma cells with reduced tumorigenicity. The ifndings by Yan etal. validate the polycomb protein enhancer of zeste homologue 2 (EZH2) as a target for intervention.

  2. The Promised Land: Moses, Nearing, Skinner, Le Guin.

    Science.gov (United States)

    Farrelly, James P.

    1981-01-01

    Perceives utopia as the quest for the promised land. Proposes such quests derive from Moses delivering his people from captivity to a new place on earth. Cites true fictional accounts enjoining the need to strive for perfection and search for a site to build a perfect society (Editor/DMM)

  3. Evaluating the Promise of the "FUSION" Tier 2 Math Intervention

    Science.gov (United States)

    Cary, Mari Strand; Doabler, Christian; Clarke, Benjamin; Fien, Hank; Baker, Scott K.; Jungjohann, Kathy J.

    2013-01-01

    The low level of mathematics performance of U.S. students in relation to national standards and in international comparisons has concerned educators and policy makers for many years. The authors' primary goals were to design a feasible and usable intervention and gather data on the promise of the intervention to foster students' conceptual…

  4. Reducing Aggressive Male Behavior in Elementary School: Promising Practices

    Science.gov (United States)

    Holmes, Barbara; Gibson, Jamel; Morrison-Danner, Dietrich

    2014-01-01

    Student aggression and violent behavior, especially among males, is pervasive and problematic in the classroom. When incorporated in the lesson design, promising practices (music, movement, and visual stimulation) are evidence-based strategies that may reduce male aggression in the classroom.

  5. The Utility, Limitations, and Promise of Proteomics in Animal Science

    Science.gov (United States)

    Proteomics experiments have the ability to simultaneously identify and quantify potentially thousands of proteins in one experiment. The use of this technology in animal science is still in its infancy, yet it holds significant promise as a method for advancing animal science research. Examples of...

  6. Parent Trigger Laws and the Promise of Parental Voice

    Science.gov (United States)

    Smith, William C.; Rowland, Julie

    2014-01-01

    Parent trigger laws have gained momentum nationally under the premise that they will increase local authority by amplifying parental voice in the decision to turn around "failing" schools. Using Hirschman's exit, voice, and loyalty framework we create two conceptual models of voice and evaluate the promise of voice in California,…

  7. Fulfilling the Promise: Do MOOCS Reach the Educationally Underserved?

    Science.gov (United States)

    Schmid, Lorrie; Manturuk, Kim; Simpkins, Ian; Goldwasser, Molly; Whitfield, Keith E.

    2015-01-01

    When massive open online courses (MOOCs) began, they held the promise of bringing high-quality, college-level courses from leading academic institutions to people who otherwise would not have access to that type of content. In the ensuing years, it has become clear that the majority of MOOC students are not underserved in terms of educational…

  8. Understanding the promises and premises of online health platforms

    NARCIS (Netherlands)

    J. van Dijck; T. Poell

    2016-01-01

    This article investigates the claims and complexities involved in the platform-based economics of health and fitness apps. We examine a double-edged logic inscribed in these platforms, promising to offer personal solutions to medical problems while also contributing to the public good. On the one ha

  9. Promising Teacher Practices: Students' Views about Their Science Learning

    Science.gov (United States)

    Moeed, Azra; Easterbrook, Matthew

    2016-01-01

    Internationally, conceptual and procedural understanding, understanding the Nature of Science, and scientific literacy are considered worthy goals of school science education in modern times. The empirical study presented here reports on promising teacher practices that in the students' views afford learning opportunities and support their science…

  10. Promising Tools for Biological Applications: Nanoparticles and Polyelectrolyte Polymer Capsules

    OpenAIRE

    Munoz, Almudena

    2008-01-01

    In this work, we address two different structures whose sizes are in the nanoscopic and microscopic range, namely nanoparticles and polyelectrolyte polymer capsules respectively. Among a wide variety of their promising applications, some are discussed. Synthesis, characterization and surface modification of semiconductor CdSe/ZnS and metallic Au nanoparticles are presented. Au nanoparticles were synthesized directly in organic sol...

  11. Dimeric Surfactants: Promising Ingredients of Cosmetics and Toiletries

    OpenAIRE

    Naveen Kumar; Rashmi Tyagi

    2013-01-01

    Surfactants are an essential ingredient for cosmetic, toiletries and personal care products for enhancing their performance. Dimeric surfactants demonstrate superiority compared to conventional surfactants in all areas of application. Dimeric surfactants are extremely promising for utilization in various cosmetic formulations viz. shampoo, lotions, creams, conditioners etc. These surfactants possess extremely unique surface properties viz. lower surface tension, unique micellization, low crit...

  12. The Math Promise: Celebrating at Home and School

    Science.gov (United States)

    Legnard, Danielle; Austin, Susan

    2014-01-01

    The Math Promise is a contract that family members make with one another. They commit to spending mathematical time together; getting to know each other's mathematical thinking and understanding; and finding time to play math games, solve problems, and notice mathematics in their daily lives. Whether parents and children are cooking in the…

  13. Photonic crystal fiber based antibody detection

    DEFF Research Database (Denmark)

    Duval, A; Lhoutellier, M; Jensen, J B; Hoiby, P E; Missier, V; Pedersen, L H; Hansen, Theis Peter; Bjarklev, Anders Overgaard; Bang, Ole

    An original approach for detecting labeled antibodies based on strong penetration photonic crystal fibers is introduced. The target antibody is immobilized inside the air-holes of a photonic crystal fiber and the detection is realized by the means of evanescent-wave fluorescence spectroscopy and...

  14. Receptor antibodies as novel therapeutics for diabetes

    DEFF Research Database (Denmark)

    Ussar, Siegfried; Vienberg, Sara Gry; Kahn, C Ronald

    2011-01-01

    Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases....

  15. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  16. Bioconjugation of antibodies to horseradish peroxidase (hrp)

    Science.gov (United States)

    The bioconjugation of an antibody to an enzymatic reporter such as horseradish peroxidase (HRP) affords an effective mechanism by which immunoassay detection of a target antigen can be achieved. The use of heterobifunctional cross—linkers to covalently link antibodies to HRP provides a simple and c...

  17. Thyrotropin receptor antibodies and its clinical application

    International Nuclear Information System (INIS)

    Thyrotropin receptor antibodies (TRAb) are not homogeneous, which are composed by four antibodies at least. TRAb plays very important roles in autoimmune thyroid diseases ad off-thyroid symptoms associated, and other thyroiditis in clinical diagnosis, assessment of curative effects, determination of the time to stop medicine, prognostication of recurrence and inspection of high risk population

  18. Monoclonal antibodies to Leptospira interrogans serovar pomona.

    OpenAIRE

    Ainsworth, A J; Lester, T L; Capley, G

    1985-01-01

    Three monoclonal antibodies produced against Leptospira interrogans serovar pomona have been studied for their diagnostic usefulness. All three monoclonals reacted strongly in the enzyme-linked immunosorbent assay and indirect fluorescent antibody test with serovar pomona and did not react with serovars grippotyphosa, canicola, icterohaemorrhagiae and hardjo.

  19. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

  20. Determination of Biotin: Antibody Molar Ratio

    International Nuclear Information System (INIS)

    The determination of the biotinylation yield (number of biotin molecules per molecule of antibody) is important to ensure that the MAb has maintained its immunoreactivity. If the biotinylation of the MAb is carried out with a molar ratio of biotin:antibody ~10:1, then the number of biotins per MAb usually ranges between 6 and 8

  1. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  2. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M. (Santa Fe, NM)

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  3. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  4. Labelling of monoclonal antibodies with 99Tcm, their quality control and evaluation for scintigraphy

    International Nuclear Information System (INIS)

    Several clinical studies have demonstrated that both the 111In and 99Tcm labelled specific monoclonal antibodies and non specific human immunoglobulins can delineate variety of cancerous infectious and inflammatory lesions. However, due to practical advantages of 99Tcm over 111In, 99Tcm labelled antibodies have exhibited distinct advantages for clinical investigations. Although the most stable and specific method for labelling antibodies with 99Tcm is performed by the bifunctional approach, there has recently been an increased interest in direct labelling methods as a result of significant improvement in the stability of the radiolabel and its potential application in the form of kits which can produce 99Tcm-antibody complex at the time of use. Direct methods based on the use of 2-mercaptoethanol ascorbic acid, borohydride and boric acid buffer appeared most promising. In addition, the method based on the use of iminothiolane to provide 99Tcm attachment site on the lysine has also been claimed a good practical method. We have evaluated these methods for radiolabelling of antibodies with 99Tcm using human immunoglobulin (hIgG) and an anti CEA mouse monoclonal antibody (ior-CEA-1) by studying labelling efficiency, in vitro serum stability, relative radionuclide binding strength, immunoreactivity, blood kinetics, biodistribution, specific target scintigraphy and also for development of lyophilized kits. The study has led to the improvement of the method based on the use o 2-ME and development of a novel method which uses ascorbic acid (ASC) to label the antibodies with 99Tcm and the production of lyophilized kits which give quality 99Tcm-hIgG and 99Tcm-ior-CEA-1 instantly when mixed with 99Tcm-pertechnetate. Both the products prepared from the kits have been found suitable for immunoscintigraphy

  5. sup(99m)Tc-labeled antibacterial antibody scan for the diagnosis of infective endocarditis (in rabbit)

    International Nuclear Information System (INIS)

    The mortality of infective endocarditis is high and the results of blood cultures and clinical manifestations may be unreliable in its diagnosis. A technique has been developed using the specific antigen-antibody reaction against sup(99m)Tc-labelled antibacterial antibody. The antibody, tagged by an electrolytic method, remained very active and was not denatured since 99% of the sup(99m)Tc-antibody was able to react with antigen. The labelled antibody was injected intravenously into rabbits with experimental aortic endocarditis. The radioactivity of the infected aortic valves was about four times greater than that in the uninfected valves. A scintillation scan was able to detect the infected valves in vivo. (U.K.)

  6. Cell Culture Microfluidic Biochips: Experimental Throughput Maximization

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan;

    2011-01-01

    Microfluidic biochips offer a promising alternative to a conventional biochemical laboratory, integrating all necessary functionalities on-chip in order to perform biochemical applications. Researchers have started to propose computer-aided design tools for the synthesis of such biochips. Our focus...... Annealing metaheuristic for experimental design generation for the cell culture microfluidic biochips, and we have evaluated our approach using multiple experimental setups....

  7. Nano antibody therapy for cancer

    International Nuclear Information System (INIS)

    Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. Nanotechnology can have an early, paradigm-changing impact on how clinicians will detect cancer in its earliest stages. Exquisitely sensitive devices constructed of nanoscale components-such as nanocantilevers, nanowires and nanochannels-offer the potential for detecting even the rarest molecular signals associated with malignancy. One of the most pressing needs in clinical oncology is for imaging agents that can identify tumors that are far smaller than is possible with today's technology, at a scale of 100,000 cells rather than 1,000,000,000 cells. A new approach in nanotechnology for treating cancer incorporates nano iron particles and attaches them to an antibody that has targets only cancer cells and not healthy cells. The treatment works in two steps. This treatment is an ingenious way to make localized tumor ablation a systemic treatment. The advantages are incredible. There are absolutely no side effects from this treatment. It is not painful or even uncomfortable. The iron particles get flushed harmlessly from the body. It is not a drug and so the cancer cannot build up a resistance to the treatment. It is a systematic treatment; even cancer cells and tumors that are not known about get heated up and ablated. This treatment can even be used to enhance imaging of the cancer because once the cancer cells are coated with the iron particles, they are easy to identify. Everything depends on how reliably the antibodies target cancer cells and not healthy cells. When used in conjunction with other systemic treatments, such as vaccine treatments, we could be looking at a time when even advanced cancers can be brought under control. (author)

  8. Synthetic Antibodies for Reversible Cell Recognition

    Science.gov (United States)

    Zhou, Jing Zhou

    2011-12-01

    Antibody-mediated cell recognition plays a critical role in various biological and biomedical applications. However, strong antibody-cell interactions can lead to the difficulty of separating antibodies from the bound cells in a simple and non-destructive manner, which is often necessary to numerous applications such as cell sorting or separation. Thus, this thesis research is aimed to create an antibody-like nanomaterial with the function of reversible cell recognition It was hypothesized that nucleic acid aptamer and dendrimer could be used as fundamental structural components to develop an antibody-like nanomaterial. The aptamer functions as the binding site of an antibody; the dendrimer is used as a robust, defined nano-scaffold to support the aptamer and to carry small molecules (e.g., fluorophores). To test this hypothesis, a novel method was first developed to discover the essential nucleotides of full-length aptamers to mimic the binding sites of antibodies. The essential nucleotides were further conjugated with a dendrimer to synthesize a monovalent aptamer-dendrimer nanomaterial. The results clearly showed that the essential nucleotides could maintain high affinity and specificity after tethered on dendrimer surface. To further test the hypothesis that antibody-like nanomaterials can be rationally designed to acquire the capability of reversible cell recognition, an aptamer that was selected at 0 °C was used as a model to synthesize a "Y-shaped" nanomaterial by conjugating two aptamers to the same dendrimer. The results showed that the nanomaterial-cell interaction could be affected by the distance between two binding aptamers. In addition, the "Y-shaped" antibody-like nanomaterial could bind target cells more strongly than its monovalent control. Importantly, the strong cell-nanomaterial interaction could be rapidly reversed when the temperature was shifted from 0 °C to 37 °C. In summary, we developed a synthetic antibody that can not only mimic the

  9. Genetically engineered multivalent single chain antibody constructs for cancer therapy

    International Nuclear Information System (INIS)

    increase its tumor: normal tissue ratio for improved therapeutic index, we engineered a variety antibody constructs. These constructs were evaluated using novel approaches like special radionuclides, pretargeting and optimization. Due to the smaller size, the engineered antibody molecules should penetrate better throughout a tumor mass, with less dose heterogeneity, than is the case with intact IgG. Multivalent scFvs with an appropriate radionuclide, therefore, hold promising prospects for cancer therapy and clinical imaging in MAb-based radiopharmaceuticals. In addition, the human anti-mouse antibodies (HAMA) responses in patients against antibody-based therapy are usually directed against the immunoglobulin constant regions; however, anti-idiotypic responses can also be detected. The HAMA responses reduce the efficacy of treatment by removing the circulating antibody molecules, fragments, and possibly scFvs by altering the pharmacokinetic properties of the antibody. HAMA responses against divalent IgG, divalent Ig fragments, and possibly multimeric scFvs could cause immune complex formation with hypersensitivity or allergic reactions that could be harmful to patients. The use of small molecules, such as scFvs (monomeric as well as multimeric), with their shorter biological half-lives and the lack of the constant regions and humanized variable (binding regions) performed in our studies should reduce the development of HAMA. The generation of humanized and fully human scFvs should further reduce the development of HAMA. Specific accomplishments on the project are the production of large amounts of recombinant antibodies as they are required in large amounts for cancer diagnosis and therapy. A variety of single-chain Fv (scFv) constructs were engineered for the desired pharmacokinetic properties. Tetrameric and dimeric scFvs showed a two-fold advantage: (1) there was a considerable gain in avidity as compared to smaller fragments, and (2) the biological half-life was more

  10. Genetically engineered multivalent single chain antibody constructs for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Surinder Batra, Ph D

    2006-02-27

    its tumor: normal tissue ratio for improved therapeutic index, we engineered a variety antibody constructs. These constructs were evaluated using novel approaches like special radionuclides, pretargeting and optimization. Due to the smaller size, the engineered antibody molecules should penetrate better throughout a tumor mass, with less dose heterogeneity, than is the case with intact IgG. Multivalent scFvs with an appropriate radionuclide, therefore, hold promising prospects for cancer therapy and clinical imaging in MAb-based radiopharmaceuticals. In addition, the human anti-mouse antibodies (HAMA) responses in patients against antibody-based therapy are usually directed against the immunoglobulin constant regions; however, anti-idiotypic responses can also be detected. The HAMA responses reduce the efficacy of treatment by removing the circulating antibody molecules, fragments, and possibly scFvs by altering the pharmacokinetic properties of the antibody. HAMA responses against divalent IgG, divalent Ig fragments, and possibly multimeric scFvs could cause immune complex formation with hypersensitivity or allergic reactions that could be harmful to patients. The use of small molecules, such as scFvs (monomeric as well as multimeric), with their shorter biological half-lives and the lack of the constant regions and humanized variable (binding regions) performed in our studies should reduce the development of HAMA. The generation of humanized and fully human scFvs should further reduce the development of HAMA. Specific accomplishments on the project are the production of large amounts of recombinant antibodies as they are required in large amounts for cancer diagnosis and therapy. A variety of single-chain Fv (scFv) constructs were engineered for the desired pharmacokinetic properties. Tetrameric and dimeric scFvs showed a two-fold advantage: (1) there was a considerable gain in avidity as compared to smaller fragments, and (2) the biological half-life was more

  11. The Promised Savior in Pre-Islamic Great Religions

    Directory of Open Access Journals (Sweden)

    Mahin Arab

    2014-09-01

    Full Text Available Since the ancient times the belief in the rise of the Reformer has been a fundamental principle. Many of the holy prophets have announced the advent of new prophet. Moreover in the announcements and indications of predecessors there are always allusions to "the Last Promised" and "the Savior of Last Days" under such titles as "Kalki", "Fifth Buddha", "Soshyans", "Messiah", "The Son of Man" and so on and so forth. Of course there are different types of belief in the last reformer in religions. In one place the Savior is merely a social reformer while in another place he is only after the spiritual salvation of people and even sometimes he undertakes both tasks. On the other hand, the Last Promised is once nationalist and once seeks to save the whole world.    This essay seeks to assay the views of pre-Islamic great religions including Zoroastrianism, Judaism, Christianity, Hinduism and Buddhism as to the Promised Savior. This essay is an analytico-descriptive research which has based itself on the first hand works comprising the sacred scriptures of religions and proceeds through the typological analyses of idea of the Promised in religions.    Zoroastrianism: the idea of the Promised has been tied to the notion of Soshyant. Generally speaking, this notion alludes to a group of people who periodically emerge at the end of every millennium of the last three millennia of world's age so as to uproot evil and renew the world, the last one of these reformers is Soshyans. According to the aforementioned typology, Zoroastrian idea of Last Savior is among the Promised who saves the whole world. Moreover Zoroastrian Promised cannot be declared only a social savior as he is not wholly detached from people's spirituality too. From another point of view, Zoroastrian idea of the Promised represents a universal and not nationalist savior who is relatively a human and not divine entity who emerges in the last millennium of world's age.    Judaism: in the

  12. Antibodies against chromosomal beta-lactamase

    DEFF Research Database (Denmark)

    Giwercman, B; Rasmussen, J W; Ciofu, Oana; Clemmentsen, I; Schumacher, H; Høiby, N

    1994-01-01

    A murine monoclonal anti-chromosomal beta-lactamase antibody was developed and an immunoblotting technique was used to study the presence of serum and sputum antibodies against Pseudomonas aeruginosa chromosomal group 1 beta-lactamase in patients with cystic fibrosis (CF). The serum antibody...... response was studied with serum samples collected in 1992 from 56 CF patients in a cross-sectional study and with serum samples from 18 CF patients in a longitudinal study. Anti-beta-lactamase immunoglobulin G antibodies were present in all of the serum samples from the patients with chronic...... bronchopulmonary P. aeruginosa infection (CF + P) but in none of the CF patients with no or intermittent P. aeruginosa infection. Anti-beta-lactamase antibodies were present in serum from CF + P patients after six antipseudomonal courses (median) and correlated with infection with a beta-lactam-resistant strain of...

  13. Antibody-Mediated Lung Transplant Rejection

    Science.gov (United States)

    Hachem, Ramsey

    2012-01-01

    Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunction have been reported, and these demonstrate that antibodies can directly injure the allograft. However, the incidence and toll of antibody-mediated rejection are unknown because there is no widely accepted definition and some cases may be unrecognized. Clearly, humoral immunity has become an important area for research and clinical investigation. PMID:23002428

  14. Antiphospholipid antibody: laboratory, pathogenesis and clinical manifestations

    Directory of Open Access Journals (Sweden)

    T. Ziglioli

    2011-06-01

    Full Text Available Antiphospholipid antibodies (aPL represent a heterogeneous group of antibodies that recognize various antigenic targets including beta2 glycoprotein I (β2GPI, prothrombin (PT, activated protein C, tissue plasminogen activator, plasmin and annexin A2. The most commonly used tests to detect aPL are: lupus anticoagulant (LAC, a functional coagulation assay, anticardiolipin antibody (aCL and anti-β2GPI antibody (anti-β2GPI, which are enzyme-linked immunoassay (ELISA. Clinically aPL are associated with thrombosis and/or with pregnancy morbidity. Apparently aPL alone are unable to induce thrombotic manifestations, but they increase the risk of vascular events that can occur in the presence of another thrombophilic condition; on the other hand obstetrical manifestations were shown to be associated not only to thrombosis but mainly to a direct antibody effect on the trophoblast.

  15. Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria

    DEFF Research Database (Denmark)

    Cavanagh, David R; Dodoo, Daniel; Hviid, Lars; Kurtzhals, Jørgen; Theander, Thor G; Akanmori, Bartholomew D; Polley, Spencer; Conway, David J; Koram, Kojo; McBride, Jana S

    2004-01-01

    This longitudinal prospective study shows that antibodies to the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP-1) are associated with protection against clinical malaria in an area of stable but seasonal malaria transmission of Ghana. Antibodies to the bl....... falciparum and, thus, a promising new candidate for the development of a malaria vaccine.......This longitudinal prospective study shows that antibodies to the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP-1) are associated with protection against clinical malaria in an area of stable but seasonal malaria transmission of Ghana. Antibodies to the...... block 2 region of MSP-1 were measured in a cohort of 280 children before the beginning of the major malaria transmission season. The cohort was then actively monitored for malaria, clinically and parasitologically, over a period of 17 months. Evidence is presented for an association between antibody...

  16. A monoclonal antibody interferes with TIMP-2 binding and incapacitates the MMP-2-activating function of multifunctional, pro-tumorigenic MMP-14/MT1-MMP

    DEFF Research Database (Denmark)

    Shiryaev, S A; Remacle, A G; Golubkov, V S; Ingvarsen, S; Porse, A; Behrendt, N; Cieplak, P; Strongin, A Y

    2013-01-01

    Matrix metalloproteinases (MMPs) and, especially membrane type 1 (MT1)-MMP/MMP-14, are promising drug targets in malignancies. In contrast with multiple small-molecule and protein pan-inhibitors of MT1-MMP cleavage activity, the murine 9E8 monoclonal antibody targets the MMP-2-activating function......, prevents tissue inhibitor of metalloproteinases-2 (TIMP-2) association with MT1-MMP. As a result, the 9E8 antibody incapacitates the TIMP-2-dependent MMP-2-activating function alone rather than the general enzymatic activity of human MT1-MMP. The specific function of the 9E8 antibody we determined directly...... its well-controlled conversion into the mature MMP-2 enzyme. In sum, understanding of the structural requirements for the 9E8 antibody specificity may pave the way for the focused design of the inhibitory antibodies against other individual MMPs....

  17. Origin of Aggregate Formation in Antibody Crystal Suspensions Containing PEG.

    Science.gov (United States)

    Hildebrandt, Christian; Mathaes, Roman; Saedler, Rainer; Winter, Gerhard

    2016-03-01

    The crystalline state of proteins is deemed as a promising formulation platform for biopharmaceuticals. However, a stabilizing effect of protein crystal suspensions is controversially discussed. In fact, antibodies can display an increased aggregation and particle formation profile after the crystallization process compared with liquid or solid amorphous formulations. Nevertheless, studies regarding aggregate formation and its origin remain meager in literature. It was the aim of this study to investigate these aspects for a model IgG antibody (mAb1), which shows an increased aggregate formation after crystallization with polyethylene glycol. The presence of a dynamic equilibrium, a steady exchange of protein between the crystals and the supernatant, was demonstrated by replacing the supernatant with an identical but fluorescence-labeled protein solution and followed by confocal laser scanning microscopy. Aggregate formation was monitored by size exclusion high-pressure chromatography and flow cytometry. Constantly increasing aggregate levels were found for the crystal fraction and for the supernatant. For the later, markedly higher particle counts were detected. The labeled supernatant and the unlabeled protein crystals allowed a precise identification of the origin of the aggregates. The rising aggregate fractions of the crystals displayed high mean fluorescence intensities that elucidated their origin in the supernatant. PMID:26886344

  18. Isolation of Balamuthia mandrillaris-specific antibody fragments from a bacteriophage antibody display library.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Kulsoom, Huma; Lalani, Salima; Khan, Naveed Ahmed

    2016-07-01

    Balamuthia mandrillaris is a protist pathogen that can cause encephalitis with a mortality rate of more than 95%. Early diagnosis followed by aggressive treatment is a pre-requisite for successful prognosis. Current methods for identifying this organism rely on culture and microscopy, antibody-based methods using animals, or involve the use of molecular tools that are expensive. Here, we describe the isolation of antibody fragments that can be used for the unequivocal identification of B. mandrillaris. B. mandrillaris-specific antibody fragments were isolated from a bacteriophage antibody display library. Individual clones were studied by enzyme-linked immunosorbent assay, and immunofluorescence. Four antibody clones showed specific binding to B. mandrillaris. The usefulness of phage antibody display technology as a diagnostic tool for isolating antibody fragments against B. mandrillaris antigens and studying their biological role(s) is discussed further. PMID:27055361

  19. Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization

    International Nuclear Information System (INIS)

    Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity

  20. Vector-Mediated In Vivo Antibody Expression.

    Science.gov (United States)

    Schnepp, Bruce C; Johnson, Philip R

    2014-08-01

    This article focuses on a novel vaccine strategy known as vector-mediated antibody gene transfer, with a particular focus on human immunodeficiency virus (HIV). This strategy provides a solution to the problem of current vaccines that fail to generate neutralizing antibodies to prevent HIV-1 infection and AIDS. Antibody gene transfer allows for predetermination of antibody affinity and specificity prior to "immunization" and avoids the need for an active humoral immune response against the HIV envelope protein. This approach uses recombinant adeno-associated viral (rAAV) vectors, which have been shown to transduce muscle with high efficiency and direct the long-term expression of a variety of transgenes, to deliver the gene encoding a broadly neutralizing antibody into the muscle. Following rAAV vector gene delivery, the broadly neutralizing antibodies are endogenously synthesized in myofibers and passively distributed to the circulatory system. This is an improvement over classical passive immunization strategies that administer antibody proteins to the host to provide protection from infection. Vector-mediated gene transfer studies in mice and monkeys with anti-HIV and simian immunodeficiency virus (SIV)-neutralizing antibodies demonstrated long-lasting neutralizing activity in serum with complete protection against intravenous challenge with virulent HIV and SIV. These results indicate that existing potent anti-HIV antibodies can be rapidly moved into the clinic. However, this methodology need not be confined to HIV. The general strategy of vector-mediated antibody gene transfer can be applied to other difficult vaccine targets such as hepatitis C virus, malaria, respiratory syncytial virus, and tuberculosis. PMID:26104192