Analytical FcRn affinity chromatography for functional characterization of monoclonal antibodies.

abstract：:The annual "Antibody Industrial Symposium", co organized by LabEx MAbImprove, MabDesign and Polepharma, was held in Tours, France on June 27-28, 2017. The focus was on antibody-drug-conjugates (ADCs), new entities which realize the hope of Paul Ehrlich's magic bullet. ADCs result from the bioconjugation of a highly cy...

journal_title：mAbs

authors： Martin C,Kizlik-Masson C,Pèlegrin A,Watier H,Viaud-Massuard MC,Joubert N

更新日期：2018-02-01 00:00:00

abstract：:Interactions between the cytoplasmic domains of viral transmembrane proteins and host machinery often determine the outcome of viral infection. The M2 protein of influenza A has been identified as a key player in autophagy-mediated viral replication. Here, we describe the engineering and validation of an antibody spec...

journal_title：mAbs

authors： Velappan N,Micheva-Viteva S,Adikari SH,Waldo GS,Lillo AM,Bradbury ARM

更新日期：2020-01-01 00:00:00

abstract：:The B cell antigen receptor repertoire is highly diverse and constantly modified by clonal selection. High-throughput DNA sequencing (HTS) of the lymphocyte repertoire (Rep-Seq) represents a promising technology to explore such diversity ex-vivo and assist in the identification of antigen-specific antibodies based on ...

journal_title：mAbs

authors： Cortina-Ceballos B,Godoy-Lozano EE,Sámano-Sánchez H,Aguilar-Salgado A,Velasco-Herrera Mdel C,Vargas-Chávez C,Velázquez-Ramírez D,Romero G,Moreno J,Téllez-Sosa J,Martínez-Barnetche J

更新日期：2015-01-01 00:00:00

abstract：:Glycosylation is an important post-translational modification during protein production in eukaryotic cells, and it is essential for protein structure, stability, half-life, and biological functions. In this study, we produced various monoclonal antibody (mAb) glycoforms from Chinese hamster ovary (CHO) cells, includi...

journal_title：mAbs

authors： Zheng K,Yarmarkovich M,Bantog C,Bayer R,Patapoff TW

更新日期：2014-05-01 00:00:00

abstract：:High physical stability is required for the development of monoclonal antibodies (mAbs) into successful therapeutic products. Developability assays are used to predict physical stability issues such as high viscosity and poor conformational stability, but protein aggregation remains a challenging property to predict. ...

journal_title：mAbs

authors： Kopp MRG,Wolf Pérez AM,Zucca MV,Capasso Palmiero U,Friedrichsen B,Lorenzen N,Arosio P

更新日期：2020-01-01 00:00:00

abstract：:Antibody-drug conjugates (ADCs) that exploit the active metabolite SN-38, which is derived from the popular anticancer drug, irinotecan (a camptothecin that inhibits the nuclear topoisomerase I enzyme, inducing double-stranded DNA breaks during the mitotic S-phase of affected cells), represent a substantial advance in...

journal_title：mAbs

authors： Goldenberg DM,Sharkey RM

更新日期：2019-08-01 00:00:00

abstract：:Multivalent mono- or bispecific antibodies are of increasing interest for therapeutic applications, such as efficient receptor clustering and activation, or dual targeting approaches. Here, we present a novel platform for the generation of Ig-like molecules, designated diabody-Ig (Db-Ig). The antigen-binding site of D...

journal_title：mAbs

authors： Seifert O,Rau A,Beha N,Richter F,Kontermann RE

更新日期：2019-07-01 00:00:00

abstract：:During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The 'zoo' of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibo...

journal_title：mAbs

authors： Brinkmann U,Kontermann RE

更新日期：2017-02-01 00:00:00

abstract：:Ectodomains of target antigens for antibody-based therapies can be shed from the target cell surface and found in sera of patients. Shed ectodomains of therapeutic targets not only pose the risk of sequestering therapeutic antibodies but, in a multimeric form, of triggering T cell activation by bispecific antibodies b...

journal_title：mAbs

authors： Petsch S,Gires O,Rüttinger D,Denzel S,Lippold S,Baeuerle PA,Wolf A

更新日期：2011-01-01 00:00:00

abstract：:Manipulation of binding affinity between monoclonal antibodies (mAbs) and the neonatal Fc receptor (FcRn) has been leveraged to extend mAb half-life; however, the steps required for success remain ambiguous and experimental observations are inconsistent. Recent models have considered the time course of endosomal trans...

journal_title：mAbs

authors： Maas BM,Cao Y

更新日期：2018-11-01 00:00:00

abstract：:The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can be considered a class property with values that are similar to endogenous IgG. Knowledge of these parameters across species could be used to avoid unnecessary in vivo PK studies and to enable early PK predictions and pharmacokinetic/pharm...

journal_title：mAbs

authors： Betts A,Keunecke A,van Steeg TJ,van der Graaf PH,Avery LB,Jones H,Berkhout J

更新日期：2018-07-01 00:00:00

abstract：:Highly concentrated antibody solutions often exhibit high viscosities, which present a number of challenges for antibody-drug development, manufacturing and administration. The antibody sequence is a key determinant for high viscosity of highly concentrated solutions; therefore, a sequence- or structure-based tool tha...

journal_title：mAbs

authors： Agrawal NJ,Helk B,Kumar S,Mody N,Sathish HA,Samra HS,Buck PM,Li L,Trout BL

更新日期：2016-01-01 00:00:00

abstract：:Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of ...

journal_title：mAbs

authors： Vana AM,Freyman AW,Reich SD,Yin D,Li R,Anderson S,Jacobs IA,Zacharchuk CM,Ewesuedo R

更新日期：2016-07-01 00:00:00

abstract：:Fragmentation in the hinge region of an IgG1 monoclonal antibody (mAb) can affect product stability, potentially causing changes in potency and efficacy. Metals ions, such as Cu(2+), can bind to the mAb and undergo hydrolysis or oxidation, which can lead to cleavage of the molecule. To better understand the mechanism ...

journal_title：mAbs

authors： Glover ZK,Basa L,Moore B,Laurence JS,Sreedhara A

更新日期：2015-01-01 00:00:00

abstract：:A mono-specific antibody may recruit a second antigen binding specificity, thus converting to a dual-specific Two-in-One antibody through mutation at the light chain complementarity-determining regions (CDRs). It is, however, unknown whether mutation at the heavy chain CDRs may evolve such dual specificity. Herein, we...

journal_title：mAbs

authors： Lee CV,Koenig P,Fuh G

更新日期：2014-05-01 00:00:00

abstract：:Bispecific antibody therapeutics can expand the functionality of a conventional monoclonal antibody drug because they can bind multiple antigens. However, their great potential is counterbalanced by the challenges faced in their production. The classic asymmetric bispecific containing an Fc requires the expression of ...

journal_title：mAbs

authors： Cooke HA,Arndt J,Quan C,Shapiro RI,Wen D,Foley S,Vecchi MM,Preyer M

更新日期：2018-11-01 00:00:00

abstract：:The neonatal Fc receptor (FcRn) promotes antibody recycling through rescue from normal lysosomal degradation. The binding interaction is pH-dependent with high affinity at low pH, but not under physiological pH conditions. Here, we combined rational design and saturation mutagenesis to generate novel antibody variants...

journal_title：mAbs

authors： Mackness BC,Jaworski JA,Boudanova E,Park A,Valente D,Mauriac C,Pasquier O,Schmidt T,Kabiri M,Kandira A,Radošević K,Qiu H

更新日期：2019-10-01 00:00:00

abstract：:Efficient production of large quantities of therapeutic antibodies is becoming a major goal of the pharmaceutical industry. We developed a proprietary expression system using a polyprotein precursor-based approach to antibody expression in mammalian cells. In this approach, the coding regions for heavy and light chain...

journal_title：mAbs

authors： Gion WR,Davis-Taber RA,Regier DA,Fung E,Medina L,Santora LC,Bose S,Ivanov AV,Perilli-Palmer BA,Chumsae CM,Matuck JG,Kunes YZ,Carson GR

更新日期：2013-07-01 00:00:00

abstract：:Accurate measurement and functional characterization of antibody Fc domain N-linked glycans is critical to successful biosimilar development. Here, we describe the application of methods to accurately quantify and characterize the N-linked glycans of 2 IgG1 biosimilars with effector function activity, and show the pot...

journal_title：mAbs

authors： Brady LJ,Velayudhan J,Visone DB,Daugherty KC,Bartron JL,Coon M,Cornwall C,Hinckley PJ,Connell-Crowley L

更新日期：2015-01-01 00:00:00

abstract：:The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types of pharmacokinetic (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab an...

journal_title：mAbs

authors： Hardiansyah D,Ng CM

更新日期：2018-10-01 00:00:00

abstract：:Certolizumab pegol (Cimzia(®)) is currently the only PEGylated anti-TNFα biologic approved for the treatment of rheumatoid arthritis and Crohn disease. The product, developed by UCB, is a humanized antigen-binding fragment (Fab') of a monoclonal antibody that has been conjugated to polyethylene glycol. Certolizumab pe...

journal_title：mAbs

authors： Goel N,Stephens S

更新日期：2010-03-01 00:00:00

abstract：:Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This antibody binds to the rat recycling receptor FcRn as expected for a human IgG1 antibody and do...

journal_title：mAbs

authors： Li B,Tesar D,Boswell CA,Cahaya HS,Wong A,Zhang J,Meng YG,Eigenbrot C,Pantua H,Diao J,Kapadia SB,Deng R,Kelley RF

更新日期：2014-01-01 00:00:00

abstract：:Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new ap...

journal_title：mAbs

authors： Fontaine FR,Goodall S,Prokop JW,Howard CB,Moustaqil M,Kumble S,Rasicci DT,Osborne GW,Gambin Y,Sierecki E,Jones ML,Zuegg J,Mahler S,Francois M

更新日期：2018-05-01 00:00:00

abstract：:Antibodies that target a clinically relevant group of receptors within the tumor necrosis factor receptor superfamily (TNFRSF), including CD40 and CD95 (Fas/Apo-1), also require binding to Fc gamma receptors (FcγRs) to elicit a strong agonistic activity. This FcγR dependency largely relies on the mere cellular anchori...

journal_title：mAbs

authors： Nelke J,Medler J,Weisenberger D,Beilhack A,Wajant H

更新日期：2020-01-01 00:00:00

abstract：:The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn's role in the metabolism of IgG within individual tissu...

journal_title：mAbs

authors： Yip V,Palma E,Tesar DB,Mundo EE,Bumbaca D,Torres EK,Reyes NA,Shen BQ,Fielder PJ,Prabhu S,Khawli LA,Boswell CA

更新日期：2014-05-01 00:00:00

abstract：:In recent years, capillary electrophoresis-sodium dodecyl sulfate (cSDS) has been widely used for high resolution separation and quantification of the fragments and aggregates of monoclonal antibodies (mAbs) to ensure the quality of mAb therapeutics. However, identification of the low-molecular-weight (LMW) and high-m...

journal_title：mAbs

authors： Wang WH,Cheung-Lau J,Chen Y,Lewis M,Tang QM

更新日期：2019-10-01 00:00:00

abstract：:Antibody engineering must be accompanied by mapping strategies focused on identifying the epitope recognized by each antibody to define its unique functional identity. High throughput fine specificity determination remains technically challenging. We review recent experiences aimed at revisiting the oldest and most ex...

journal_title：mAbs

authors： Rojas G,Tundidor Y,Infante YC

更新日期：2014-01-01 00:00:00

abstract：:Monoclonal antibodies (mAbs) are a burgeoning class of therapeutics, with more than 25 approved in countries worldwide. Novel molecules are entering clinical study at a rate of nearly 40 per year, and the commercial pipeline includes approximately 240 mAb therapeutics in clinical studies that have not yet progressed t...

journal_title：mAbs

authors： Reichert JM

更新日期：2010-01-01 00:00:00

abstract：:Genetically encoded fluorescent antibodies are desirable for many applications in biotechnology, proteomics, microscopy, cell biology and molecular diagnostics, although efficient production of fluorescent IgGs in mammalian cells has been hampered by different and mutually incompatible secretion- and folding-requireme...

journal_title：mAbs

authors： Haas AK,von Schwerin C,Matscheko D,Brinkmann U

更新日期：2010-11-01 00:00:00

abstract：:Colorectal cancer represents the second most common cause of cancer-related death. The human A33 transmembrane glycoprotein is a validated tumor-associated antigen, expressed in 95% of primary and metastatic colorectal cancers. Using phage display technology, we generated a human monoclonal antibody (termed A2) specif...

journal_title：mAbs

authors： Murer P,Plüss L,Neri D

更新日期：2020-01-01 00:00:00