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Monoclonal peak

Qing Li, Jason B White, Norman C Peterson, Keith W Rickert, Christopher O Lloyd, Kevin L Allen, Kim Rosenthal, Xizhe Gao, Herren Wu, William F Dall'Acqua, M Jack Borrok, Ping Tsui
The accumulation, dissemination and clearance of monoclonal antibody-based therapeutics or imaging reagents targeting tumor associated antigens is governed by several factors including affinity, size, charge, and valency. Tumor targeting antibody fragments have distinct advantages over intact monoclonal antibodies such as enhanced penetration within the tumor and rapid accumulation but are subject to rapid clearance. Polyethylene glycol (PEG)-modified antibody fragments can provide a way to balance tumor penetration and accumulation with improved serum persistence...
April 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Cory King, Rekha Patel, Gomathinayagam Ponniah, Christine Nowak, Alyssa Neill, Zhenyu Gu, Hongcheng Liu
In-depth characterization of the commonly observed variants is critical to the successful development of recombinant monoclonal antibody therapeutics. Multiple peaks of a recombinant monoclonal antibody were observed when analyzed by hydrophobic interaction chromatography and imaged capillary isoelectric focusing. The potential modification causing the heterogeneity was localized to F(ab')2 region by analyzing the antibody after IdeS digestion using hydrophobic interaction chromatography. LC-MS analysis identified asparagine deamidation as the root cause of the observed multiple variants...
April 3, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Balázs Bobály, Matthew Lauber, Alain Beck, Davy Guillarme, Szabolcs Fekete
A wide-pore silica-based superficially porous material with a high coverage phenyl bonding was evaluated for the analysis of monoclonal antibodies and antibody-drug conjugates. This new material is based on 2.7 μm particles having a shell thickness of 0.40 μm and average pore size of approximately 450 Å. Various important features of this reversed phase column technology were explored, including kinetic performance for large biomolecules (i.e. speed of analysis, efficiency and peak capacity), recovery of proteins, selectivity for resolving modifications, and the possibility to reduce the amount of trifluoroacetic acid in the mobile phase...
March 21, 2018: Journal of Chromatography. A
Chen Zheng, Chao Zhuang, Jinyan Qin, Yantian Chen, Qiang Fu, Hui Qian, Tong Wu, Yanchao Wang, Xiang Wu, Nianmin Qi
Charge heterogeneity has been broadly studied as a critical quality attribute during monoclonal antibody (mAb) production that may subsequently affect product stability and biopotency. However, the charge variation distribution is poorly controlled, so methods of more effective control need to be explored. In this study, the combined effects of temperature shift (37-34, 37-32, or 37-30 °C) and hydrolysate addition (0.100 g/L) to culture feed on the charge heterogeneity of anti-IgE mAb were investigated. The results showed that the distribution of charge variation was significantly regulated by the combination of hydrolysate addition with a highly sub-physiological temperature (34 °C)...
March 27, 2018: Cytotechnology
Kevin Hollevoet, Elien De Smidt, Nick Geukens, Paul Declerck
Antibody gene transfer presents an appealing alternative to conventional antibody protein therapy. This pre-clinical study evaluates the impact of various parameters on the pharmacokinetics and efficacy of in vivo expressed DNA-based anti-HER2 monoclonal antibodies (mAbs), newly engineered and delivered via intramuscular electrotransfer in mice. Plasma concentrations of trastuzumab and 4D5, its murine IgG1 equivalent, peaked on average between 1-15 µg/ml, depending on the administration and configuration of the encoding plasmid DNA (pDNA)...
March 2, 2018: Oncotarget
Deepti Ahluwalia, Madesh Belakavadi, Tapan K Das, Amit Katiyar
Product identity is one of the release testing requirements that needs to be established to ensure that there is no misidentification of drugs. Here, we demonstrated the challenges that can come across while establishing a product identity method for monoclonal antibody (mAb) and mAb-related products using icIEF method. A unique three-point identity criteria tool (visual comparison, pI of individual peaks and ΔpIs) was applied to distinguish mAb1 from the other in-house mAbs. A reduction approach followed by icIEF showed higher potential for establishing identity for mAb1 product as compared to native and enzymatic digestion approach...
March 1, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Thomas Theis, Anmol Singh Johal, Maciej Kabat, Sayantani Basak, Melitta Schachner
Glycosylation fine-tunes signal transduction of adhesion molecules during neural development and supports synaptic plasticity and repair after injury in the adult nervous system. One abundantly expressed neural glycan is LewisX (LeX). Although it is known that its expression starts at the formation of the neural tube during the second embryonic week in the mouse and peaks during the first postnatal week, its functional relevance is only rudimentarily understood. To gain better insights into the functions of this glycan, we identified small organic compounds that mimic structurally and functionally this glycan glycosidically linked to several neural adhesion molecules...
March 8, 2018: Molecular Neurobiology
Latifa Mohammadi, Noria Harir, Mohamed Brahimi, Soraya Moulessehoul, Mohamed Amine Bekadja
BACKGROUND: Multiple Myeloma (MM) represent about 1 to 2% of cancers and 15% of all hematological malignancies. It is characterized by malignant proliferation of plasmocytes in bone marrow and an excess of secreted monoclonal immunoglobulins (Ig) Objective: Describe the epidemiological, clinical, biological and prognosis of patients with MM treated with autologous peripheral hematopoietic stem cell transplantation (APHSCT) in the Algerian West. METHODS: It is a retrospective descriptive study covering all MM patients treated with APHSCT over a period of 7 years (2008-2015) at service of Haematology and Cell Therapy of the EHU "1er November 1954 of Oran, Algeria...
June 2017: La Tunisie Médicale
Nissreen Mohammad, Vishal Avinashi, Edmond Chan, Bruce A Vallance, Elodie Portales-Casamar, Jonathan W Bush
OBJECTIVE: Eosinophilic esophagitis (EoE) is considered a TH2-mediated food allergy disease that leads to submucosal esophageal fibrosis and strictures. Recent studies focused on adults with EoE identified a strong association with elevated esophageal IgG4 immunostaining. Our study aimed to determine the association of IgG4 with EoE in pediatric patients. METHODS: Using our local EoE research registry, we identified 41 adequate biopsies from EoE patients. We used 10 age- and sex-matched patients with no diagnostic abnormalities at endoscopy or on biopsy...
March 5, 2018: Journal of Pediatric Gastroenterology and Nutrition
Staci L Haney, Yashpal S Chhonker, Michelle L Varney, Geoffrey Talmon, Daryl J Murry, Sarah A Holstein
Geranylgeranyl diphosphate synthase (GGDPS) is the enzyme in the isoprenoid biosynthesis pathway that catalyzes the synthesis of the 20-carbon isoprenoid GGPP, which serves as the isoprenoid donor for protein geranylgeranylation reactions. Rab proteins mediate vesicle trafficking within the cell and their activity is dependent on geranylgeranylation. Our prior work has demonstrated that agents that disrupt Rab geranylgeranylation disrupt monoclonal protein trafficking in myeloma cells, resulting in induction of the unfolded protein response pathway and apoptosis...
March 2, 2018: Investigational New Drugs
Diaddin Hamdan, François Darrouzain, Theodora Bejan-Angoulvant, Charles Isorni, Laurent Zelek, Gilles Paintaud, Anne Janin, Guilhem Bousquet
PURPOSE: Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule...
April 2018: Cancer Chemotherapy and Pharmacology
Mun Peak Nyon, Lanying Du, Chien-Te Kent Tseng, Christopher A Seid, Jeroen Pollet, Kevin S Naceanceno, Anurodh Agrawal, Abdullah Algaissi, Bi-Hung Peng, Wanbo Tai, Shibo Jiang, Maria Elena Bottazzi, Ulrich Strych, Peter J Hotez
Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals...
February 26, 2018: Vaccine
Florian Füssl, Ken Cook, Kai Scheffler, Amy Farrell, Stefan Mittermayr, Jonathan Bones
Charge variant analysis (CVA) of monoclonal antibodies (mAbs) using cation exchange chromatography is routinely used as a fingerprint of the distribution of posttranslational modifications present on the molecule. Traditional salt or pH based eluents are not suited for direct coupling to mass spectrometry due to non-volatility or high ionic strength. This makes further analysis complicated when an alteration in the charge variant profile or the emergence of an additional peak is encountered. Here, the use of pH gradient elution using volatile, low ionic strength buffers is reported with direct coupling to high resolution Orbitrap™ mass spectrometry...
March 1, 2018: Analytical Chemistry
Alexey Ruzin, Yuling Wu, Li Yu, Xiang-Qing Yu, David E Tabor, Hoyin Mok, Christine Tkaczyk, Kathryn Jensen, Terramika Bellamy, Lorin Roskos, Mark T Esser, Hasan S Jafri
Objectives: MEDI4893 is a novel, long-acting human monoclonal antibody targeting Staphylococcus aureus (SA) alpha toxin (AT). This report presents the results of the exploratory analyses from a randomised phase 1 dose-escalation study in healthy human subjects receiving single intravenous MEDI4893 doses or placebo. Methods: Anti-AT antibodies and AT expression were measured as described previously. Nasal swabs were analysed by culture and PCR. Data were summarised by treatment groups and visits by using SAS System Version 9...
2018: Clinical & Translational Immunology
Yi Feng Lee, Matthias Jöhnck, Christian Frech
The efficiencies of mono gradient elution and dual salt-pH gradient elution for separation of six mAb charge and size variants on a preparative-scale ion exchange chromatographic resin are compared in this study. Results showed that opposite dual salt-pH gradient elution with increasing pH gradient and simultaneously decreasing salt gradient is best suited for the separation of these mAb charge and size variants on Eshmuno® CPX. Besides giving high binding capacity, this type of opposite dual salt-pH gradient also provides better resolved mAb variant peaks and lower conductivity in the elution pools compared to single pH or salt gradients...
February 21, 2018: Biotechnology Progress
Wendy Bernhard, Ayman El-Sayed, Kris Barreto, Carolina Gonzalez, Wayne Hill, Angel Casaco Parada, Humphrey Fonge, C Ronald Geyer
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Near infrared (NIR) fluorescent dye-labeled antibodies represent an attractive class of image-guided surgical probes because of their high specificity, tumor uptake, and low dissociation from tumor cells that express the antigen. In this study, we developed a NIR fluorescent dye-labeled nimotuzumab immunoconjugate, IRDye800CW-nimotuzumab, and evaluated in vitro binding with EGFR-positive cells, in vivo tumor uptake by NIR fluorescent imaging, and ex vivo biodistribution...
January 19, 2018: Oncotarget
Ole Wilhelm Bøe, Kjell Sveen, Magne Børset, Kirk M Druey
BACKGROUND Systemic capillary leak syndrome (SCLS) (Clarkson's disease) is a rare disorder of unknown etiology, characterized by transient episodes of hypotension, and the microvascular leak of fluids into the peripheral tissues, resulting in edema. Between 80-90% of patients with SCLS have a concomitant monoclonal gammopathy. Although translational in vitro studies have implicated vascular endothelial barrier dysfunction in the etiology of SCLS, the etiology and disease associations in clinical cases remain unknown...
February 16, 2018: American Journal of Case Reports
Jingjie Mo, Renzhe Jin, Qingrong Yan, Izabela Sokolowska, Michael J Lewis, Ping Hu
Glycation has been observed in antibody therapeutics manufactured by the fed-batch fermentation process. It not only increases the heterogeneity of antibodies, but also potentially affects product safety and efficacy. In this study, non-glycated and glycated fractions enriched from a monoclonal antibody (mAb1) as well as glucose-stressed mAb1 were characterized using a variety of biochemical, biophysical and biological assays to determine the effects of glycation on the structure and function of mAb1. Glycation was detected at multiple lysine residues and reduced the antigen binding activity of mAb1...
February 13, 2018: MAbs
Abigail Turner, Katharina Yandrofski, Srivalli Telikepalli, Jason King, Alan Heckert, James Filliben, Dean Ripple, John E Schiel
The NISTmAb is a monoclonal antibody Reference Material from the National Institute of Standards and Technology; it is a class-representative IgG1κ intended to serve as a pre-competitive platform for harmonization and technology development in the biopharmaceutical industry. The publication series of which this paper is a part describes NIST's overall control strategy to ensure NISTmAb quality and availability over its lifecycle. In this paper, the development of a control strategy for monitoring NISTmAb size heterogeneity is described...
February 10, 2018: Analytical and Bioanalytical Chemistry
Trina Mouchahoir, John E Schiel
Peptide mapping is a component of the analytical toolbox used within the biopharmaceutical industry to aid in the identity confirmation of a protein therapeutic and to monitor degradative events such as oxidation or deamidation. These methods offer the advantage of providing site-specific information regarding post-translational and chemical modifications that may arise during production, processing or storage. A number of such variations may also be induced by the sample preparation methods themselves which may confound the ability to accurately evaluate the true modification levels...
February 7, 2018: Analytical and Bioanalytical Chemistry
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