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Human Monoclonal antibodies

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https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#1
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28719385/prevention-of-hemolytic-disease-of-the-fetus-and-newborn-what-have-we-learned-from-animal-models
#2
Yoelys Cruz-Leal, Danielle Marjoram, Alan H Lazarus
PURPOSE OF REVIEW: This review aims to highlight recent advances in our understanding of how anti-red blood cell (RBC) antibodies prevent erythrocyte immunization with an emphasis on new murine models. RECENT FINDINGS: New murine models with clinically relevant human erythrocyte antigens have been used to understand the alloimmunization process and its inhibition. The search to elucidate the mechanism of action of IgG-mediated inhibition of erythrocyte alloimmunization has provided new evidence in support of a potential role for epitope masking, immune deviation and/or antigen modulation in this process...
July 17, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28717038/a-human-biofilm-disrupting-monoclonal-antibody-potentiates-antibiotic-efficacy-in-rodent-models-of-both-staphylococcus-aureus-and-acinetobacter-baumannii-infections
#3
Yan Q Xiong, Angeles Estellés, L Li, W Abdelhady, R Gonzales, Arnold S Bayer, Edgar Tenorio, Anton Leighton, Stefan Ryser, Lawrence M Kauvar
Many serious bacterial infections are antibiotic-refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high affinity human monoclonal antibody against a DNABII epitope conserved across both gram-positive and gram-negative bacterial species. In the current study, the efficacy of TRL1068 for disruption of biofilm was demonstrated in vitro in the absence of antibiotics by scanning electron microscopy...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28716913/antibody-based-assay-discriminates-zika-virus-infection-from-other-flaviviruses
#4
Angel Balmaseda, Karin Stettler, Raquel Medialdea-Carrera, Damaris Collado, Xia Jin, José Victor Zambrana, Stefano Jaconi, Elisabetta Cameroni, Saira Saborio, Francesca Rovida, Elena Percivalle, Samreen Ijaz, Steve Dicks, Ines Ushiro-Lumb, Luisa Barzon, Patricia Siqueira, David W G Brown, Fausto Baldanti, Richard Tedder, Maria Zambon, A M Bispo de Filippis, Eva Harris, Davide Corti
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716900/structural-insights-into-the-extracellular-recognition-of-the-human-serotonin-2b-receptor-by-an-antibody
#5
Andrii Ishchenko, Daniel Wacker, Mili Kapoor, Ai Zhang, Gye Won Han, Shibom Basu, Nilkanth Patel, Marc Messerschmidt, Uwe Weierstall, Wei Liu, Vsevolod Katritch, Bryan L Roth, Raymond C Stevens, Vadim Cherezov
Monoclonal antibodies provide an attractive alternative to small-molecule therapies for a wide range of diseases. Given the importance of G protein-coupled receptors (GPCRs) as pharmaceutical targets, there has been an immense interest in developing therapeutic monoclonal antibodies that act on GPCRs. Here we present the 3.0-Å resolution structure of a complex between the human 5-hydroxytryptamine 2B (5-HT2B) receptor and an antibody Fab fragment bound to the extracellular side of the receptor, determined by serial femtosecond crystallography with an X-ray free-electron laser...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#6
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28713391/apoptosis-induced-via-gamma-delta-t-cell-antigen-receptor-blocking-antibodies-a-cautionary-tale
#7
Indrani Dutta, Lynne-Marie Postovit, Gabrielle M Siegers
Mechanistic studies contribute greatly to our understanding of γδ T cell (γδTc) biology, aiding development of these cells as immunotherapeutic agents. The antibody blocking assay is an accepted method to determine the receptors involved in γδTc killing of tumor targets. Effectors and/or targets are preincubated with microgram quantities of monoclonal antibodies (mAb), often described by commercial sources to be useful for blocking assays. We and others have used such assays extensively in the past, correlating decreases in cytotoxicity against specific targets with involvement of the blocked receptor(s)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#8
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713010/hemolectin-expression-reveals-functional-heterogeneity-in-honey-bee-apis-mellifera-hemocytes
#9
Erika Gábor, Gyöngyi Cinege, Gábor Csordás, Tibor Török, Katalin Folkl-Medzihradszky, Zsuzsanna Darula, István Andó, Éva Kurucz
The identification of molecular markers considerably facilitated the classification and functional analysis of blood cell types. Apis mellifera hemocytes have been classified by morphological criteria and lectin binding properties; however, the use of molecular markers has been minimal. Here we describe a monoclonal antibody to a non-phagocytic subpopulation of A. mellifera hemocytes and to a constituent of the hemolymph clot. We demonstrate that the antibody identifies the A. mellifera hemolectin, a protein carrying human von Willebrand factor homology domains, characteristic of proteins involved in blood coagulation and platelet aggregation in mammals...
July 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28710803/expression-of-the-major-vault-protein-mvp-and-cellular-vault-particles-in-fish
#10
Alyssa L Margiotta, Lisa J Bain, Charles D Rice
Cellular vaults are ubiquitous 13 mega Da multi-subunit ribonuceloprotein particles that may have a role in nucleocytoplasmic transport. Seventy percent of the vault's mass consists of a ≈100 kDa protein, the major vault protein. In humans, a drug resistance -associated protein, originally identified as lung resistance protein in metastatic lung cancer, was ultimately shown to be the previously described major vault protein. In this study, a partial major vault protein sequence was cloned from channel catfish...
July 15, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28708993/il-4r%C3%AE-inhibitor-for-atopic-disease
#11
Howard Y Chang, Kari C Nadeau
Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4Rα subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was approved for use in the treatment of atopic dermatitis (eczema). To view this Bench to Bedside, open or download the PDF.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28707668/-low-molecular-weight-regulators-of-biogenic-polyamine-metabolism-affect-cytokine-production-and-expression-of-hepatitis-%C3%B0-virus-proteins-in-huh7-5-human-hepatocarcinoma-cells
#12
O V Masalova, E I Lesnova, E I Samokhvalov, K Yu Permyakova, A V Ivanov, S N Kochetkov, A A Kushch
Hepatitis C virus (HCV) induces the expression of the genes of proinflammatory cytokines, the excessive production of which may cause cell death, and contribute to development of liver fibrosis and hepatocarcinoma. The relationship between cytokine production and metabolic disorders in HCV-infected cells remains obscure. The levels of biogenic polyamines, spermine, spermidine, and their precursor putrescine, may be a potential regulator of these processes. The purpose of the present work was to study the effects of the compounds which modulate biogenic polyamines metabolism on cytokine production and HCV proteins expression...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28707587/immunotherapeutic-interleukin-6-or-interleukin-6-receptor-blockade-in-cancer-challenges-and-opportunities
#13
Nirmala C Kampan, Sue D Xiang, Orla M McNally, Andrew N Stephens, Michael A Quinn, Magdalena Plebanski
Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signaling pathway has become a target for the therapy of in diverse cancers such as multicentric Castleman's disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28707278/daclizumab-development-clinical-trials-and-practical-aspects-of-use-in-multiple-sclerosis
#14
REVIEW
Laura E Baldassari, John W Rose
Daclizumab is a humanized monoclonal antibody directed towards CD25, the alpha subunit of the high-affinity interleukin (IL)-2 receptor. Daclizumab exerts its effects via multiple mechanisms, including reduction of IL-2-mediated lymphocyte activation and upregulation of CD56-bright natural killer cells. Intravenous daclizumab (Zenapax™) was initially approved for prevention of rejection in renal transplant. In subsequent early testing, followed by larger-scale phase II and phase III trials, both intravenous and subcutaneous daclizumab have demonstrated clinical efficacy in the treatment of multiple sclerosis...
July 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28706506/identification-of-brca1-as-a-potential-biomarker-for-insulin-like-growth-factor-1-receptor-targeted-therapy-in-breast-cancer
#15
Tali Cohen-Sinai, Zoya Cohen, Haim Werner, Raanan Berger
The insulin-like growth factor-1 receptor (IGF1R) emerged in recent years as a promising therapeutic target in oncology. Identification of potential biomarkers capable of predicting response to IGF1R-targeted therapy is of cardinal importance. Tumor suppressor BRCA1 has important roles in multiple pathways, including gene transcription, DNA damage repair, and control of apoptosis. Early studies have identified the IGF1R gene as a downstream target for inhibitory regulation by wild-type, but not mutant, BRCA1...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28706158/significant-benefit-of-nivolumab-treating-pd-l1-positive-metastatic-pulmonary-carcinosarcoma-a-case-report-and-literature-review
#16
Zhe Zhang, Yishan Chen, Mingxia Ma, Junli Hao, Rui Ding, Lixin Han, Jiayun Zou, Lina Zhang, Qin Meng, Xiujuan Qu, Yunpeng Liu, Mingfang Zhao
Immunotherapy has recently become a new focus for the treatment of malignant tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its ligand (PD-L1), restoring the immune response of T cells, and enhancing the recognition of tumor cells by the immune system.Pulmonary Carcinosarcoma is an uncommon but highly aggressive tumor type with a poor prognosis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705932/use-of-a-neutralizing-antibody-helps-identify-structural-features-critical-for-binding-of-clostridium-difficile-toxin-tcda-to-the-host-cell-surface
#17
Heather K Kroh, Ramyavardhanee Chandrasekaran, Kim Rosenthal, Rob Woods, Xiaofang Jin, Melanie D Ohi, Andrew C Nyborg, G Jonah Rainey, Paul Warrener, Benjamin W Spiller, D Borden Lacy
Clostridium difficile is a clinically significant pathogen that causes mild-to-severe (and often recurrent) colon infections. Disease symptoms stem from the activities of two large, multi-domain toxins known as TcdA and TcdB. The toxins can bind, enter, and perturb host cell function through a multi-step mechanism of receptor binding, endocytosis, pore formation, autoproteolysis, and glucosyltransferase-mediated modification of host substrates. Monoclonal antibodies that neutralize toxin activity provide a survival benefit in preclinical animal models and prevent recurrent infections in human clinical trials...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28704111/incomplete-dabigatran-reversal-with-idarucizumab
#18
Aaron P Steele, Jin A Lee, William E Dager
CONTEXT: With increasing use of direct oral anticoagulants (DOACs), urgent reversal of these agents becomes a growing concern. Idarucizumab is a humanized monoclonal antibody fragment that specifically binds to dabigatran with higher affinity than thrombin, rapidly neutralizing its anticoagulant effect without increased risk of thrombosis. CASE DETAILS: We describe two cases in which the recommended dose of idarucizumab was unsuccessful in completely reversing the anticoagulant effects of dabigatran...
July 13, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28703903/dosage-optimization-of-nemolizumab-using-population-pharmacokinetic-and-pharmacokinetic-pharmacodynamic-modeling-and-simulation
#19
Tomohisa Saito, Satofumi Iida, Kimio Terao, Yuji Kumagai
Nemolizumab is a humanized anti-interleukin-31 receptor A monoclonal antibody for treating atopic dermatitis, and it especially improves pruritus. The objective of the simulation study was to optimize the dose regimen using a flat dose. The serum nemolizumab concentration and pruritus visual analog scale as an efficacy end point were modeled using the population analysis approach in 299 patients with atopic dermatitis who received placebo or doses between 0.1 and 3 mg/kg as a single dose once every 4 weeks or 2 mg/kg once every 8 weeks...
July 13, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28701403/monoclonal-antibodies-derived-from-humans-vaccinated-with-the-rv144-hiv-vaccine-containing-the-hvem-binding-domain-of-herpes-simplex-virus-hsv-glycoprotein-d-neutralize-hsv-infection-mediate-adcc-and-protect-mice-from-ocular-challenge-with-hsv-1
#20
Kening Wang, Georgia D Tomaras, Sinthujan Jegaskanda, M Anthony Moody, Hua-Xin Liao, Kyle Goodman, Phillip W Berman, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Barton F Haynes, Jeffrey I Cohen
The RV144 HIV vaccine trial included a recombinant HIV glycoprotein 120 (gp120) construct fused to a small portion of herpes simplex virus (HSV-1) glycoprotein D (gD), such that the first 40 amino acids of gp120 were replaced by the signal sequence and the first 27 amino acids of the mature form of gD. This region of gD contains most of the binding site for HVEM, an HSV receptor important for virus infection of epithelial cells and lymphocytes. RV144 induced antibodies to HIV that were partially protective against infection as well as antibodies to HSV...
July 12, 2017: Journal of Virology
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