An accelerated surface-mediated stress assay of antibody instability for developability studies.

abstract：:Surface and interfacial adsorption of antibody molecules could cause structural unfolding and desorbed molecules could trigger solution aggregation, resulting in the compromise of physical stability. Although antibody adsorption is important and its relevance to many mechanistic processes has been proposed, few techni...

journal_title：mAbs

authors： Smith C,Li Z,Holman R,Pan F,Campbell RA,Campana M,Li P,Webster JR,Bishop S,Narwal R,Uddin S,van der Walle CF,Lu JR

更新日期：2017-04-01 00:00:00

abstract：:While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to th...

journal_title：mAbs

authors： Derfus GE,Dizon-Maspat J,Broddrick JT,Velayo AC,Toschi JD,Santuray RT,Hsu SK,Winter CM,Krishnan R,Amanullah A

更新日期：2014-05-01 00:00:00

abstract：:Much data support a role for central nervous system antigen-specific antibodies in the pathogenesis of multiple sclerosis (MS). The effects of inducing a decrease in (auto)antibody levels on MS or experimental autoimmune encephalomyelitis (EAE) through specific blockade of FcRn, however, remain unexplored. We recently...

journal_title：mAbs

authors： Challa DK,Bussmeyer U,Khan T,Montoyo HP,Bansal P,Ober RJ,Ward ES

更新日期：2013-09-01 00:00:00

abstract：:Fusion proteins combining oligomeric assemblies of a genetically obtained single-chain (sc) variant of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with antibodies directed against tumor-associated antigens represent a promising strategy to overcome the limited therapeutic activity of conventional s...

journal_title：mAbs

authors： Siegemund M,Seifert O,Zarani M,Džinić T,De Leo V,Göttsch D,Münkel S,Hutt M,Pfizenmaier K,Kontermann RE

更新日期：2016-07-01 00:00:00

abstract：:Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs)...

journal_title：mAbs

authors： Avery LB,Wang M,Kavosi MS,Joyce A,Kurz JC,Fan YY,Dowty ME,Zhang M,Zhang Y,Cheng A,Hua F,Jones HM,Neubert H,Polzer RJ,O'Hara DM

更新日期：2016-08-01 00:00:00

abstract：:Post-translational modifications can have a signification effect on antibody stability. A comprehensive approach is often required to best understand the underlying reasons the modification affects the antibody's potency or aggregation state. Monoclonal antibody 001 displayed significant variation in terms of potency,...

journal_title：mAbs

authors： McSherry T,McSherry J,Ozaeta P,Longenecker K,Ramsay C,Fishpaugh J,Allen S

更新日期：2016-05-01 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：:Immunoglobulins and T cell receptors (TCRs) share common sequences and structures. With the goal of creating novel bispecific antibodies (BsAbs), we generated chimeric molecules, denoted IgG_TCRs, where the Fv regions of several antibodies were fused to the constant domains of the α/β TCR. Replacing CH1 with Cα and CL...

journal_title：mAbs

authors： Wu X,Sereno AJ,Huang F,Zhang K,Batt M,Fitchett JR,He D,Rick HL,Conner EM,Demarest SJ

更新日期：2015-01-01 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：:Vedolizumab (VDZ) is a humanized monoclonal antibody in development for the treatment of inflammatory bowel disease. VDZ binds to the α4β7 integrin complex and inhibits its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), thus preventing lymphocyte extravasation to gut mucosal tissues. To understand w...

journal_title：mAbs

authors： Wyant T,Yang L,Fedyk E

更新日期：2013-11-01 00:00:00

abstract：:Site-specific antibody-drug conjugates (ADCs) are designed to overcome the heterogeneity observed with first-generation ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. Despite significantly enhanced homogeneity, however, the production of site-specific ...

journal_title：mAbs

authors： Cao M,De Mel N,Jiao Y,Howard J,Parthemore C,Korman S,Thompson C,Wendeler M,Liu D

更新日期：2019-08-01 00:00:00

abstract：:The neonatal Fc receptor (FcRn) is important for the metabolic fate of IgG antibodies in vivo. Analysis of the interaction between FcRn and IgG in vitro might provide insight into the structural and functional integrity of therapeutic IgG that may affect pharmacokinetics (PK) in vivo. We developed a standardized pH gr...

journal_title：mAbs

authors： Schlothauer T,Rueger P,Stracke JO,Hertenberger H,Fingas F,Kling L,Emrich T,Drabner G,Seeber S,Auer J,Koch S,Papadimitriou A

更新日期：2013-07-01 00:00:00

abstract：:Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal anti...

journal_title：mAbs

authors： Shen Y,Zeng L,Zhu A,Blanc T,Patel D,Pennello A,Bari A,Ng S,Persaud K,Kang YK,Balderes P,Surguladze D,Hindi S,Zhou Q,Ludwig DL,Snavely M

更新日期：2013-05-01 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：: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：:Ch-mAb7F9, a human-mouse chimeric monoclonal antibody (mAb) designed to bind (+)-methamphetamine (METH) with high affinity and specificity, was produced as a treatment medication for METH abuse. In these studies, we present the preclinical characterization that provided predictive evidence that ch-mAb7F9 may be safe a...

journal_title：mAbs

authors： Stevens MW,Tawney RL,West CM,Kight AD,Henry RL,Owens SM,Gentry WB

更新日期：2014-03-01 00:00:00

abstract：:Monoclonal antibody (mAb) candidates from high-throughput screening or binding affinity optimization often contain mutations leading to liabilities for further development of the antibody, such as aggregation-prone regions and lack of solubility. In this work, we optimized a candidate integrin α11-binding mAb for deve...

journal_title：mAbs

authors： Jetha A,Thorsteinson N,Jmeian Y,Jeganathan A,Giblin P,Fransson J

更新日期：2018-08-01 00:00:00

abstract：:We describe protein synthesis, folding and assembly of antibody fragments and full-length aglycosylated antibodies using an Escherichia coli-based open cell-free synthesis (OCFS) system. We use DNA template design and high throughput screening at microliter scale to rapidly optimize production of single-chain Fv (scFv...

journal_title：mAbs

authors： Yin G,Garces ED,Yang J,Zhang J,Tran C,Steiner AR,Roos C,Bajad S,Hudak S,Penta K,Zawada J,Pollitt S,Murray CJ

更新日期：2012-03-01 00:00:00

abstract：:Structural characterization of proteins and their antigen complexes is essential to the development of new biologic-based medicines. Amino acid-specific covalent labeling (CL) is well suited to probe such structures, especially for cases that are difficult to examine by alternative means due to size, complexity, or in...

journal_title：mAbs

authors： Kaur P,Tomechko SE,Kiselar J,Shi W,Deperalta G,Wecksler AT,Gokulrangan G,Ling V,Chance MR

更新日期：2015-01-01 00:00:00

abstract：:We describe here the identification of a stop codon TAA (Stop) → GAA (Glu) = Stop221E mutation on the light chain of a recombinant IgG1 antibody expressed in a Chinese hamster ovary (CHO) cell line. The extended light chain variants, which were caused by translation beyond the mutated stop codon to the next alternativ...

journal_title：mAbs

authors： Zhang T,Huang Y,Chamberlain S,Romeo T,Zhu-Shimoni J,Hewitt D,Zhu M,Katta V,Mauger B,Kao YH

更新日期：2012-11-01 00:00:00

abstract：:Antibodies provide immune protection by recognizing antigens of diverse chemical properties, but elucidating the amino acid sequence-function relationships underlying the specificity and affinity of antibody-antigen interactions remains challenging. We designed and constructed phage-displayed synthetic antibody librar...

journal_title：mAbs

authors： Jian JW,Chen HS,Chiu YK,Peng HP,Tung CP,Chen IC,Yu CM,Tsou YL,Kuo WY,Hsu HJ,Yang AS

更新日期：2019-02-01 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：: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：:Complex cellular targets such as G protein-coupled receptors (GPCRs), ion channels, and other multi-transmembrane proteins represent a significant challenge for therapeutic antibody discovery, primarily because of poor stability of the target protein upon extraction from cell membranes. To assess whether a limited set...

journal_title：mAbs

authors： Scott MJ,Jowett A,Orecchia M,Ertl P,Ouro-Gnao L,Ticehurst J,Gower D,Yates J,Poulton K,Harris C,Mullin MJ,Smith KJ,Lewis AP,Barton N,Washburn ML,de Wildt R

更新日期：2020-01-01 00:00:00

abstract：:MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with programmed cell death-1 (PD-1) and B7.1. It is being investigated as a potential therapy for locally advanced or metastatic malignancies. The purpose ...

journal_title：mAbs

authors： Deng R,Bumbaca D,Pastuskovas CV,Boswell CA,West D,Cowan KJ,Chiu H,McBride J,Johnson C,Xin Y,Koeppen H,Leabman M,Iyer S

更新日期：2016-01-01 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：:Tremendous knowledge has been gained in the understanding of various modifications of IgG antibodies, driven mainly by the fact that antibodies are one of the most important groups of therapeutic molecules and because of the development of advanced analytical techniques. Recombinant monoclonal antibody (mAb) therapeut...

journal_title：mAbs

authors： Liu H,Ponniah G,Zhang HM,Nowak C,Neill A,Gonzalez-Lopez N,Patel R,Cheng G,Kita AZ,Andrien B

更新日期：2014-01-01 00:00:00

abstract：:The current standard treatment for acute myeloid leukemia (AML) is chemotherapy based on cytarabine and daunorubicine (7 + 3), but it discriminates poorly between malignant and benign cells. Dose-limiting off‑target effects and intrinsic drug resistance result in the inefficient eradication of leukemic blast cells and...

journal_title：mAbs

authors： Fitting J,Blume T,Ten Haaf A,Blau W,Gattenlöhner S,Tur MK,Barth S

更新日期：2015-01-01 00:00:00

abstract：:The importance of antibodies in activating immune responses against tumors is now better appreciated with the emergence of checkpoint blockade antibodies and with engineered antibody Fc domains featuring enhanced capacity to focus potent effector cells against cancer cells. Antibodies designed with Fc regions of the I...

journal_title：mAbs

authors： Josephs DH,Spicer JF,Karagiannis P,Gould HJ,Karagiannis SN

更新日期：2014-01-01 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