Phage display-based generation of novel internalizing antibody fragments for immunotoxin-based treatment of acute myeloid leukemia.

abstract：:Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics. Their design involves a tumor-specific antibody, a linker and a cytotoxic payload. They were designed to allow specific targeting of highly potent cytotoxic agents to tumor cells whilst sparing normal cells. Frequent toxicities that may be d...

journal_title：mAbs

authors： Donaghy H

更新日期：2016-05-01 00:00:00

abstract：:Process intensification has shown great potential to increase productivity and reduce costs in biomanufacturing. This case study describes the evolution of a manufacturing process from a conventional processing scheme at 1000-L scale (Process A, n = 5) to intensified processing schemes at both 1000-L (Process B, n = 8...

journal_title：mAbs

authors： Xu J,Xu X,Huang C,Angelo J,Oliveira CL,Xu M,Xu X,Temel D,Ding J,Ghose S,Borys MC,Li ZJ

更新日期：2020-01-01 00:00:00

abstract：:High titer (>10 g/L) monoclonal antibody (mAb) cell culture processes are typically achieved by maintaining high viable cell densities over longer culture durations. A corresponding increase in the solids and sub-micron cellular debris particle levels are also observed. This higher burden of solids (≥15%) and sub-micr...

journal_title：mAbs

authors： McNerney T,Thomas A,Senczuk A,Petty K,Zhao X,Piper R,Carvalho J,Hammond M,Sawant S,Bussiere J

更新日期：2015-01-01 00:00:00

abstract：:A dual-specific, tetravalent immunoglobulin G-like molecule, termed dual variable domain immunoglobulin (DVD-Ig™), is engineered to block two targets. Flexibility modulates Fc receptor and complement binding, but could result in undesirable cross-linking of surface antigens and downstream signaling. Understanding the ...

journal_title：mAbs

authors： Correia I,Sung J,Burton R,Jakob CG,Carragher B,Ghayur T,Radziejewski C

更新日期：2013-05-01 00:00:00

abstract：:Multispecific antibody formats provide a promising platform for the development of novel therapeutic concepts that could facilitate the generation of safer, more effective pharmaceuticals. However, the production and use of such antibody-based multispecifics is often made complicated by: 1) the instability of the anti...

journal_title：mAbs

authors： Egan TJ,Diem D,Weldon R,Neumann T,Meyer S,Urech DM

更新日期：2017-01-01 00:00:00

abstract：:Recombinant antibody single-chain variable fragments (scFv) are difficult to purify homogeneously from a protein complex mixture. The most effective, specific and fastest method of purification is an affinity chromatography on Protein L (PpL) matrix. This protein is a multi-domain bacterial surface protein that is abl...

journal_title：mAbs

authors： Lakhrif Z,Pugnière M,Henriquet C,di Tommaso A,Dimier-Poisson I,Billiald P,Juste MO,Aubrey N

更新日期：2016-01-01 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：: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) is a key membrane protein that plays an integral role in serum immunoglobulin (IgG) recycling, which extends the half-life of antibody. In addition, FcRn is known to traffic antigen-bound immunoglobulins (Ag-IgGs), and to interact with immune complexes to facilitate the antigen cross-pr...

journal_title：mAbs

authors： Sun Y,Estevez A,Schlothauer T,Wecksler AT

更新日期：2020-01-01 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：:Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or TRAIL-receptor agonistic monoclonal antibodies promote apoptosis in most cancer cells, and the differential expression of TRAIL-R2 between tumor and normal tissues allows its exploitation as a tumor-associated antigen. The use of thes...

journal_title：mAbs

authors： Satta A,Mezzanzanica D,Caroli F,Frigerio B,Di Nicola M,Kontermann RE,Iacovelli F,Desideri A,Anichini A,Canevari S,Gianni AM,Figini M

更新日期：2018-10-01 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：:The American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference Short Course "Translational Challenges in Developing Antibody-Drug Conjugates (ADCs)," held May 24, 2012 in San Diego, CA, was organized by members of the Pharmacokinetics, Pharmacodynamics and Drug Metabolism section of AAP...

journal_title：mAbs

authors： Thudium K,Bilic S,Leipold D,Mallet W,Kaur S,Meibohm B,Erickson H,Tibbitts J,Zhao H,Gupta M

更新日期：2013-01-01 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

abstract：:The critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients in whom IgE neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total IgE levels or body mass. In this study, we sought...

journal_title：mAbs

authors： Cohen ES,Dobson CL,Käck H,Wang B,Sims DA,Lloyd CO,England E,Rees DG,Guo H,Karagiannis SN,O'Brien S,Persdotter S,Ekdahl H,Butler R,Keyes F,Oakley S,Carlsson M,Briend E,Wilkinson T,Anderson IK,Monk PD,von Wachenfe

更新日期：2014-05-01 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：: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 to an IgG Fc region is an established strategy to extend the half-life of therapeutic proteins. Most Fc fusion proteins, however, do not achieve the long half-life of IgGs. Based on findings that scFv-Fc fusion proteins exhibit a shorter half-life than the corresponding IgG molecules, we performed a comparative...

journal_title：mAbs

authors： Unverdorben F,Richter F,Hutt M,Seifert O,Malinge P,Fischer N,Kontermann RE

更新日期：2016-01-01 00:00:00

abstract：:The importance of the neonatal Fc receptor (FcRn) in extending the serum half-life of monoclonal antibodies (mAbs) is well demonstrated, and has led to the development of multiple engineering approaches designed to alter Fc interactions with FcRn. Recent reports have additionally highlighted the effect of nonspecific ...

journal_title：mAbs

authors： Kelly RL,Yu Y,Sun T,Caffry I,Lynaugh H,Brown M,Jain T,Xu Y,Wittrup KD

更新日期：2016-10-01 00:00:00

abstract：:Ang1 is a soluble ligand to receptor Tie2, and increasing the circulating Ang1 level may improve vascular stabilization under certain disease conditions. Here, we found that the circulating Ang1 level was significantly increased in cynomolgus monkeys treated with non-neutralizing anti-Ang1 antibodies. Improving the an...

journal_title：mAbs

authors： Zheng C,Toth J,Bigwarfe T,MacDougall M,Jerath K,Bovat K,Smith J,Sun P,Hayes D,Fryer R,Singh S,Kroe-Barrett R

更新日期：2018-11-01 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：: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：:Self-interaction of an antibody may lead to aggregation, low solubility or high viscosity. Rapid identification of highly developable leads remains challenging, even though progress has been made with the introduction of techniques such as self-interaction chromatography (SIC) and cross-interaction chromatography (CIC...

journal_title：mAbs

authors： Sun T,Reid F,Liu Y,Cao Y,Estep P,Nauman C,Xu Y

更新日期：2013-11-01 00:00:00

abstract：:In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resista...

journal_title：mAbs

authors： Wang C,He X,Zhou B,Li J,Li B,Qian W,Hou S,Wang H,Shi Y,Guo Y

更新日期：2011-01-01 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：:Despite availability of biologic therapies, limited patient access to many of the most-effective cancer treatments affects overall health outcomes. To address this issue, many governments have enacted legislation for the approval of biosimilars. The term "biosimilar" refers to a biologic product that is developed to b...

journal_title：mAbs

authors： Socinski MA,Curigliano G,Jacobs I,Gumbiner B,MacDonald J,Thomas D

更新日期：2015-01-01 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：: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：: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：:The plasticity of natural immunoglobulin repertoires can be exploited for the generation of phage display libraries. Secondary lymphoid organs, such as the spleen and the lymph nodes, constitute interesting sources of diversity because they are rich in B cells, part of which can be affinity matured. These organs, howe...

journal_title：mAbs

authors： Venet S,Kosco-Vilbois M,Fischer N

更新日期：2013-09-01 00:00:00