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Human Monoclonal antibodies

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https://www.readbyqxmd.com/read/28636502/monoclonal-antibody-tx94-human-dnax-accessory-molecule-1-cd226
#1
(no author information available yet)
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June 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28634748/exposure-response-relationship-of-ramucirumab-in-east-asian-patients-from-rainbow-a-randomized-clinical-trial-in-second-line-treatment-of-gastric-cancer
#2
Tae You Kim, Chia-Jui Yen, Salah-Eddin Al-Batran, David Ferry, Ling Gao, Yanzhi Hsu, Rebecca Cheng, Mauro Orlando, Atsushi Ohtsu
BACKGROUND: Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m(2) paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure-response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial...
June 20, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28634654/improvement-in-latent-variable-indirect-response-modeling-of-multiple-categorical-clinical-endpoints-application-to-modeling-of-guselkumab-treatment-effects-in-psoriatic-patients
#3
Chuanpu Hu, Bruce Randazzo, Amarnath Sharma, Honghui Zhou
Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23...
June 20, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28634589/hla-class-ia-and-ib-polyreactive-anti-hla-e-igg2a-monoclonal-antibodies-tfl-006-and-tfl-007-suppress-anti-hla-igg-production-by-cd19-b-cells-and-proliferation-of-cd4-t-cells-while-upregulating-tregs
#4
REVIEW
Mepur H Ravindranath
The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28634480/fc-galactosylation-of-human-immunoglobulin-gamma-isotypes-improves-c1q-binding-and-enhances-complement-dependent-cytotoxicity
#5
Benjamin Peschke, Christian W Keller, Patrick Weber, Isaak Quast, Jan D Lünemann
Binding of the complement component C1q to the CH2 domain of antigen-bound immunoglobulin gamma (IgG) activates the classical complement pathway and depends on its close proximity to Fc fragments of neighboring antibodies. IgG subclasses contain a highly conserved asparagine 297 (N)-linked biantennary glycan within their CH2 domains, the core structure of which can be extended with terminal galactose and sialic acid residues. To investigate whether Fc-glycosylation regulates effector functions of human IgG subclasses, we cloned the antigen-binding region of the CD20-specific monoclonal antibody rituximab into IgG isotype expression vectors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634192/a-new-enzyme-linked-immunosorbent-assay-system-for-human-serum-hepatic-triglyceride-lipase
#6
Kazuya Miyashita, Katsuyuki Nakajima, Isamu Fukamachi, Yuji Muraba, Takafumi Koga, Yohnosuke Shimomura, Tetsuyo Machida, Masami Murakami, Junji Kobayashi
There is no previously established method for measuring human hepatic triglyceride lipase (HTGL) concentration in serum. In this study, we developed new monoclonal antibodies (MoAb mouse 9A1, MoAb rat 141A1) that react with both HTGL in serum and in post-heparin plasma (PHP) and established a novel enzyme-linked immunosorbent assay (ELISA) system for measuring serum HTGL as well as PHP-HTGL concentrations. To confirm the specificity of MoAb, we performed an immunoprecipitation -immunoblotting analysis. Both MoAb mouse 9A1and MoAb rat 141 A1 were able to immunoprecipitate not only recombinant HTGL and PHP-HTGL but also serum HTGL, demonstrating that HTGL exists in serum obtained without heparin injection...
June 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28633988/a-cross-clade-h5n1-influenza-a-virus-neutralizing-monoclonal-antibody-binds-to-a-novel-epitope-within-the-vestigial-esterase-domain-of-hemagglutinin
#7
Subha Sankar Paul, Chee-Keng Mok, Tze-Minn Mak, Oi-Wing Ng, James Odame Aboagye, Teddy John Wohlbold, Florian Krammer, Yee-Joo Tan
The sporadic outbreaks of highly pathogenic H5N1 avian influenza virus have raised public health concerns. Monoclonal antibodies (MAbs) against hemagglutinin (HA) have been increasingly used successfully for therapeutic purposes. Previously, MAb 9F4, generated against clade 1 H5N1 HA, was observed to have cross-clade neutralizing efficacy and inhibited viral entry by preventing the pH-mediated conformational change of HA. Furthermore, mouse-human chimeric MAb 9F4 was found to retain high degrees of neutralizing activity...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#8
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28631631/ki-67-evaluation-in-breast-cancer-the-daily-diagnostic-practice
#9
Lukasz Fulawka, Agnieszka Halon
CONTEXT: Breast cancer is the most common malignancy in females. It is routinely classified according to the WHO histological typing. However, there is also a molecular classification of breast cancer which is routinely substituted with surrogate subtypes based on expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors and proliferation index (PI). PI is defined as the percentage of Ki-67-positive cells among overall cell population. The method commonly applied by pathologists to determine PI is visual scoring of the sample...
April 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28630381/antibody-response-to-human-extracellular-her2-subdomain-proteins-in-mice
#10
Fateme Sadri-Ardalani, Moslem Ahmadi, Azam Hemmati, Shaghayegh Emami, Samira Farid, Mohammad Mehdi Amiri, Mahmood Jeddi-Tehrani, Mahdi Shabani, Fazel Shokri
BACKGROUND: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 protein boosting. In the present study, we evaluated the immunogenicity of different HER2 extracellular subdomains for the induction of anti-HER2 antibody response in BALB/c mice. OBJECTIVE: To investigate and characterize antibody responses to human recombinant proteins of HER2 extracellular subdomains in immunized mice...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28630122/eculizumab-blocks-vaccine-induced-opsonophagocytic-killing-of-meningococci-by-whole-blood-from-immunized-adults
#11
Monica Konar, Dan M Granoff
Eculizumab, a humanized anti-complement C5 monoclonal antibody for treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome, blocks the terminal complement pathway required for serum bactericidal activity (SBA). Because treated patients are at >1000-fold increased risk of meningococcal disease, vaccination is recommended, but whether vaccination can protect by opsonophagocytic activity in the absence of SBA is not known. Meningococci were added to anticoagulated blood from 12 healthy adults vaccinated with meningococcal serogroup B and serogroup A,C,W,Y vaccines...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28629988/4-azidocytidine-r1479-inhibits-henipaviruses-and-other-paramyxoviruses-with-high-potency
#12
Anne L Hotard, Biao He, Stuart T Nichol, Christina F Spiropoulou, Michael K Lo
The henipaviruses Nipah virus and Hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. Despite the availability of a licensed equine Hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. To explore the possibility of developing small-molecule nucleoside inhibitors against henipaviruses, we evaluated the antiviral activity of 4'-azidocytidine (R1479), a drug previously identified to inhibit flaviviruses, against henipaviruses along with other representative members of the family Paramyxoviridae...
June 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28629323/fetal-death-in-utero-and-miscarriage-in-a-patient-with-crohn-s-disease-under-therapy-with-ustekinumab-case-report-and-review-of-the-literature
#13
C Venturin, S Nancey, P Danion, M Uzzan, M Chauvenet, C Bergoin, X Roblin, B Flourié, G Boschetti
BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage...
June 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28628776/3d-printed-lattices-as-an-activation-and-expansion-platform-for-t-cell-therapy
#14
Bahman Delalat, Frances Harding, Batjargal Gundsambuu, Elena M De-Juan-Pardo, Felix M Wunner, Marie-Luise Wille, Marek Jasieniak, Kristen A L Malatesta, Hans J Griesser, Antonio Simula, Dietmar W Hutmacher, Nicolas H Voelcker, Simon C Barry
One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation...
June 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#15
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28627280/the-targeting-effect-of-hm2e8b-nctd-liposomes-on-b-lineage-leukemia-stem-cells-is-associated-with-the-hlf-slug-axis
#16
Jingying Zhang, Diyin Shen, Min Jia, Haizhao Zhao, Yongmin Tang
To identify an agent with specific activity against B-lineage leukemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanized anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b-NCTD-liposomes). These liposomes were specially designed to recognize and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b-NCTD-liposomes selectively ablated B-LSCs through targeting hepatic leukemia factor (HLF), which is implicated in hematopoietic stem cell regulation and is overexpressed in LSCs...
June 19, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28626773/hla-epitopes-the-targets-of-monoclonal-and-alloantibodies-defined
#17
REVIEW
Nadim El-Awar, Vadim Jucaud, Anh Nguyen
Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28626406/late-onset-inflammatory-bowel-disease-like-syndrome-after-ipilimumab-therapy-a-case-report
#18
Reem Akel, Bilal Anouti, Arafat Tfayli
BACKGROUND: Antitumor immunotherapy has become a major player in cancer therapy. Ipilimumab is a humanized monoclonal antibody against the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an important downregulator of T-cell activation. Ipilimumab has demonstrated tumor regression and improvement in overall survival in patients with metastatic melanoma. Unfortunately, immune activation induced by this drug has been associated with several immune-mediated adverse effects, namely diarrhea and colitis...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28626166/efficacy-of-denosumab-for-osteoporosis-in-three-female-patients-with-osteogenesis-imperfecta
#19
Masashi Uehara, Yukio Nakamura, Jun Takahashi, Mikio Kamimura, Shota Ikegami, Takako Suzuki, Shigeharu Uchiyama, Tomomi Yamaguchi, Tomoki Kosho, Hiroyuki Kato
Osteogenesis imperfecta (OI) is an inherited bone disorder that causes fractures due to impaired production of collagen type I. In recent years, denosumab, a human monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), has become widely used as an anti-osteoclastic agent for osteoporosis. This study investigated osteoporotic cases of OI to examine effects of denosumab on bone fragility. This was a retrospective, consecutive case series that included 3 female patients aged 42, 40, and 14 years, respectively...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28625864/a-systematic-study-of-the-effect-of-low-ph-acid-treatment-on-anti-drug-antibodies-specific-for-a-domain-antibody-therapeutic-impact-on-drug-tolerance-assay-sensitivity-and-post-validation-method-assessment-of-ada-in-clinical-serum-samples
#20
Uma Kavita, Jia Duo, Sean Crawford, Rong Liu, Joan Valcin, Carol Gleason, Huijin Dong, Snaehal Gadkari, Robert W Dodge, Renuka Pillutla, Binodh S DeSilva
We developed a homogeneous bridging anti-drug antibody (ADA) assay on an electro chemiluminescent immunoassay (ECLIA) platform to support the immunogenicity evaluation of a dimeric domain antibody (dAb) therapeutic in clinical studies. During method development we evaluated the impact of different types of acid at various pH levels on polyclonal and monoclonal ADA controls of differing affinities and on/off rates. The data shows for the first time that acids of different pH can have a differential effect on ADA of various affinities and this in turn impacts assay sensitivity and drug tolerance as defined by these surrogate controls...
June 15, 2017: Journal of Immunological Methods
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