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Monoclonal antibodie

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https://www.readbyqxmd.com/read/28441093/catching-the-evader-can-monoclonal-antibodies-interfere-with-staphylococcus-aureus-immune-escape
#1
Jean-Philippe Rasigade
No abstract text is available yet for this article.
April 25, 2017: Virulence
https://www.readbyqxmd.com/read/28440948/novel-reduction-sensitive-micellar-nanoparticles-assembled-from-rituximab-doxorubicin-conjugates-as-smart-and-intuitive-drug-delivery-systems-for-the-treatment-of-non-hodgkin-s-lymphoma
#2
Huabin Yin, Tong Meng, Ling Shu, Min Mao, Lei Zhou, Haiyan Chen, Dianwen Song
In this study, a novel reduction-sensitive drug delivery system, the Rituximab-Doxorubicin (RTX-DOX) micellar nanoparticle (RDMN), was specially designed for targeted delivery and release of DOX in Non-Hodgkin's Lymphoma (NHL) cells. The RDMN was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs), which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an anti-CD20 monoclonal antibody) and hydrophobic DOXs by a reduction-responsive linker, 3-(2-Pyridyldithio) propionyl hydrazide (PDPH)...
April 25, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28440781/immunohistochemical-detection-of-the-braf-v600e-mutation-in-papillary-thyroid-carcinoma-evaluation-against-real-time-polymerase-chain-reaction
#3
Miguel Paja Fano, Aitziber Ugalde Olano, Elena Fuertes Thomas, Amelia Oleaga Alday
INTRODUCTION: The BRAF V600E mutation is the most common genetic change in papillary thyroid carcinoma and is associated with a poorer clinical course. Usual methods for its study (DNA sequencing or molecular test based on PCR) are expensive and time-consuming. Recently, immunohistochemistry (IHC) for BRAF mutation has been introduced. OBJECTIVE: To compare the results of IHC and real time PCR (RT-PCR) in the detection of BRAF V600E mutation in papillary thyroid carcinoma...
February 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28440708/towards-in-vitro-to-in-vivo-translation-of-monoclonal-antibody-pharmacokinetics-application-of-a-neonatal-fc-receptor-mediated-transcytosis-assay-to-understand-the-interplaying-clearance-mechanisms
#4
Claudia A Castro Jaramillo, Sara Belli, Anne-Christine Cascais, Sherri Dudal, Martin R Edelmann, Markus Haak, Marie-Elise Brun, Michael B Otteneder, Mohammed Ullah, Christoph Funk, Franz Schuler, Silke Simon
Monoclonal antibodies (mAbs) are a rapidly growing drug class for which great efforts have been made to optimize certain molecular features in order to achieve the desired pharmacokinetic (PK) properties. One approach is to engineer the interactions of the mAb with the neonatal Fc receptor (FcRn) by introducing specific amino acid sequence mutations, and to assess their effect on the PK profile with in vivo studies. Indeed, FcRn protects mAbs from intracellular degradation, thereby prolongs antibody circulation time in plasma and modulates its systemic clearance...
April 25, 2017: MAbs
https://www.readbyqxmd.com/read/28440620/water-proton-nmr-a-tool-for-protein-aggregation-characterization
#5
Marc B Taraban, Roberto A DePaz, Brian Lobo, Yihua Bruce Yu
Formulation stability is a critical attribute of any protein-based biopharmaceutical drug due to a protein's inherent tendency to aggregate. Advanced analytical techniques currently used for characterization of protein aggregates are prone to a number of limitations, and usually require additional manipulations with the sample, such as dilution, separation, labeling and use of special cuvettes. In the present work, we compared conventional techniques for the analysis of protein aggregates with a novel approach that employs the water proton transverse relaxation rate R2(1H2O)...
April 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28440561/anterior-st-elevation-myocardial-infarction-induced-by-rituximab-infusion-a-case-report-and-review-of-the-literature
#6
K Sharif, A Watad, N L Bragazzi, E Asher, A Abu Much, Y Horowitz, M Lidar, Y Shoenfeld, H Amital
WHAT IS KNOWN AND OBJECTIVES: Rituximab is a chimeric monoclonal anti-CD20 antibody approved for the treatment of some lymphoid malignancies as well as for autoimmune diseases including rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and vasculitis. Generally, rituximab is well tolerated; nevertheless, some patients develop adverse effects including infusion reactions. Albeit rare, these reactions may in some cases be life-threatening conditions. Rituximab cardiovascular side effects include more common effects such as hypertension, oedema and rare cases of arrhythmias and myocardial infarction...
June 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28440223/structural-insights-into-the-molecular-mechanisms-of-myasthenia-gravis-and-their-therapeutic-implications
#7
Kaori Noridomi, Go Watanabe, Melissa N Hansen, Gye Won Han, Lin Chen
The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28440060/a-practical-approach-in-bioreactor-scale-up-and-process-transfer-using-a-combination-of-constant-p-v-and-vvm-as-the-criterion
#8
Sen Xu, Linda Hoshan, Rubin Jiang, Balrina Gupta, Eric Brodean, Kristin O'Neill, T Craig Seamans, John Bowers, Hao Chen
Bioreactor scale-up is a critical step in the production of therapeutic proteins such as monoclonal antibodies (MAbs). With the scale-up criterion such as similar power input per volume or O2 volumetric mass transfer coefficient (kL a), adequate oxygen supply and cell growth can be largely achieved. However, CO2 stripping in the growth phase is often inadequate. This could cascade down to increased base addition and osmolality, as well as residual lactate increase and compromised production and product quality...
April 25, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28439933/effect-of-anti-ige-in-occupational-asthma-caused-by-exposure-to-low-molecular-weight-agents
#9
M Ollé-Monge, M J Cruz, S Gomez-Ollés, I Ojanguren, J Vanoirbeek, X Muñoz
BACKGROUND: The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In the present study we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts. METHODS: On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18 and 21 animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline...
April 25, 2017: Allergy
https://www.readbyqxmd.com/read/28439930/detection-and-identification-of-platelet-antibodies-using-a-sensitive-multiplex-assay-system-platelet-antibody-bead-array
#10
Krista Metzner, Julie Bauer, Heather Ponzi, Allison Ujcich, Brian R Curtis
BACKGROUND: Tests for platelet-specific antibodies are important in the diagnosis of immune platelet disorders. Monoclonal antibody glycoprotein capture assays have been the gold standards in platelet antibody detection for almost 30 years. However, such assays are complex and cumbersome to perform, which limits their routine use. We report the performance of a newly developed, easy to perform platelet antibody bead array (PABA) for the detection of platelet-specific antibodies. STUDY DESIGN AND METHODS: PABA is the equivalent of the monoclonal antigen capture enzyme-linked immunosorbent assay (ELISA) (MACE) on a bead and instead with fluorescent detection of immunoglobulin (Ig)G platelet antibodies by Luminex...
April 25, 2017: Transfusion
https://www.readbyqxmd.com/read/28439919/motor-polyradiculopathy-during-pembrolizumab-treatment-of-metastatic-melanoma
#11
Maria Sepúlveda, Eugenia Martinez-Hernandez, Lydia Gaba, Ivan Victoria, Nuria Sola-Valls, Neus Falgàs, Jordi Casanova-Molla, Francesc Graus
INTRODUCTION: Pembrolizumab, a monoclonal antibody directed against the immune checkpoint PD-1 (programmed cell death-1 receptor), has improved survival in patients with advanced melanoma. Neuromuscular immune-mediated side effects have been rarely reported. METHODS: We describe a 44-year-old man with metastatic melanoma who presented with progressive muscle weakness after 23 doses of pembrolizumab. RESULTS: The patient developed asymmetric, proximal muscle weakness and atrophy in all four limbs...
April 25, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28439883/an-update-for-richter-syndrome-new-directions-and-developments
#12
REVIEW
Toby A Eyre, Anna Schuh
High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439844/therapeutic-efficacy-of-%C3%AE-radioimmunotherapy-with-different-activity-levels-of-the-213-bi-labeled-monoclonal-antibody-mx35-in-an-ovarian-cancer-model
#13
Anna Gustafsson-Lutz, Tom Bäck, Emma Aneheim, Ragnar Hultborn, Stig Palm, Lars Jacobsson, Alfred Morgenstern, Frank Bruchertseifer, Per Albertsson, Sture Lindegren
BACKGROUND: The aim of this study was to compare the therapeutic efficacy of two different activity levels of the (213)Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of (213)Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28439684/impact-of-altered-endogenous-igg-on-unspecific-mab-clearance
#14
Saskia Fuhrmann, Charlotte Kloft, Wilhelm Huisinga
Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major process influencing the unspecific clearance of endogenous and therapeutic IgG. The concentration of endogenous IgG in immunodeficient mice, however is reduced, and this effect on the FcRn protection mechanism and subsequently on unspecific mAb clearance is unknown, yet of great importance for the interpretation of mAb PK data...
April 24, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28439623/identification-of-multiple-sources-of-the-acidic-charge-variants-in-an-igg1-monoclonal-antibody
#15
Shiwei Miao, Panpan Xie, Mao Zou, Li Fan, Xuping Liu, Yan Zhou, Liang Zhao, Ding Ding, Haibin Wang, Wen-Song Tan
Charge variants, especially acidic charge variants, of recombinant monoclonal antibodies are the major critical quality attributes in the biotechnology industry due to their potential influence on stability and biological activity. The chemical properties of the acidic charge variants have been challenging to fully characterize, and it is critical for process development and optimization. To completely understand the multiple sources of acidic charge variants, the major charge forms of an IgG1 monoclonal antibody were firstly isolated and then analyzed by a battery of characterization tools...
April 24, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28439081/long-lasting-neutralization-of-c5-by-sky59-a-novel-recycling-antibody-is-a-potential-therapy-for-complement-mediated-diseases
#16
Taku Fukuzawa, Zenjiro Sampei, Kenta Haraya, Yoshinao Ruike, Meiri Shida-Kawazoe, Yuichiro Shimizu, Siok Wan Gan, Machiko Irie, Yoshinori Tsuboi, Hitoshi Tai, Tetsushi Sakiyama, Akihisa Sakamoto, Shinya Ishii, Atsuhiko Maeda, Yuki Iwayanagi, Norihito Shibahara, Mitsuko Shibuya, Genki Nakamura, Takeru Nambu, Akira Hayasaka, Futa Mimoto, Yuu Okura, Yuji Hori, Kiyoshi Habu, Manabu Wada, Takaaki Miura, Tatsuhiko Tachibana, Kiyofumi Honda, Hiroyuki Tsunoda, Takehisa Kitazawa, Yoshiki Kawabe, Tomoyuki Igawa, Kunihiro Hattori, Junichi Nezu
Dysregulation of the complement system is linked to the pathogenesis of a variety of hematological disorders. Eculizumab, an anti-complement C5 monoclonal antibody, is the current standard of care for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). However, because of high levels of C5 in plasma, eculizumab has to be administered biweekly by intravenous infusion. By applying recycling technology through pH-dependent binding to C5, we generated a novel humanized antibody against C5, SKY59, which has long-lasting neutralization of C5...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439022/structure-of-a-protective-epitope-of-group-b-streptococcus-type-iii-capsular-polysaccharide
#17
Filippo Carboni, Roberto Adamo, Monica Fabbrini, Riccardo De Ricco, Vittorio Cattaneo, Barbara Brogioni, Daniele Veggi, Vittoria Pinto, Irene Passalacqua, Davide Oldrini, Rino Rappuoli, Enrico Malito, Immaculada Y Ros Margarit, Francesco Berti
Despite substantial progress in the prevention of group B Streptococcus (GBS) disease with the introduction of intrapartum antibiotic prophylaxis, this pathogen remains a leading cause of neonatal infection. Capsular polysaccharide conjugate vaccines have been tested in phase I/II clinical studies, showing promise for further development. Mapping of epitopes recognized by protective antibodies is crucial for understanding the mechanism of action of vaccines and for enabling antigen design. In this study, we report the structure of the epitope recognized by a monoclonal antibody with opsonophagocytic activity and representative of the protective response against type III GBS polysaccharide...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438600/neurotrophin-receptors-in-the-pathogenesis-diagnosis-and-therapy-of-neurodegenerative-diseases
#18
REVIEW
Jacopo Meldolesi
In the last few years, exciting properties have emerged regarding the activation, signaling, mechanisms of action, and therapeutic targeting of the two types of neurotrophin receptors: the p75(NTR) with its intracellular and extracellular peptides, the Trks, their precursors and their complexes. This review summarizes these new developments, with particular focus on neurodegenerative diseases. Based on the evolving knowledge, innovative concepts have been formulated regarding the pathogenesis of these diseases, especially the Alzheimer's and two other, the Parkinson's and Huntington's diseases...
April 21, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28438386/catabolism-of-antibody-drug-conjugates-and-characterization-methods
#19
REVIEW
Mohammad Shadid, Stephen Bowlin, Jayaprakasam Bolleddula
Antibody drug conjugates (ADCs) are large molecule therapeutics in which a cytotoxic payload is conjugated to a monoclonal antibody (mAb) via a linker. The molecules are designed to selectively bind to target-expressing cells, thus delivering therapeutic agents directly to the tumor. Chemical and enzymatic stability prior to reaching the target is an important factor for ADCs since it impacts their safety, efficacy, and pharmacokinetics (PK). One of the main reasons for off-target effects of ADCs is premature release of cytotoxic agents, either in the blood stream or at non-specific sites...
April 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28438082/radioimmunoconjugates-for-treating-cancer-recent-advances-and-current-opportunities
#20
Mickaël Bourgeois, Clément Bailly, Mathieu Frindel, François Guerard, Michel Chérel, Alain Faivre-Chauvet, Françoise Kraeber-Bodéré, Caroline Bodet-Milin
Radioimmunoconjugates have been used for 30 years to diagnose and treat cancer. For many years, the use of these therapeutic tools has been limited to haematological disorders, such as non-Hodgkin's lymphoma, given that they have only had a moderate effect on solid tumours. Areas covered: Recently, several strategies have revived the potential therapeutic application for radioimmunoconjugates. In this review, the authors review the advances in immunological engineering to develop new tools like monoclonal antibodies and their derivatives...
April 24, 2017: Expert Opinion on Biological Therapy
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