Site-specific antibody-drug conjugate heterogeneity characterization and heterogeneity root cause analysis.

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：:One aspiration for the formulation of human monoclonal antibodies (mAb) is to reach high solution concentrations without compromising stability. Protein surface activity leading to instability is well known, but our understanding of mAb adsorption to the solid-liquid interface in relevant pH and surfactant conditions ...

journal_title：mAbs

authors： Couston RG,Skoda MW,Uddin S,van der Walle CF

更新日期：2013-01-01 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：:Phage display library technology is a common method to produce human antibodies. In this technique, the immunoglobulin variable regions are displayed in a bacteriophage in a way that each filamentous virus displays the product of a single antibody gene on its surface. From the collection of different phages, it is pos...

journal_title：mAbs

authors： Sotelo P,Collazo N,Zuñiga R,Gutiérrez-González M,Catalán D,Ribeiro CH,Aguillón JC,Molina MC

更新日期：2012-07-01 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：: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：:Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e...

journal_title：mAbs

authors： Dimitrov DS

更新日期：2009-01-01 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：: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：: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：:Monoclonal antibodies (mAb) have become a mainstay in tumor therapy. Clinical responses to mAb therapy, however, are far from optimal, with many patients presenting native or acquired resistance or suboptimal responses to a mAb therapy. MAbs exert antitumor activity through different mechanisms of action and we propos...

journal_title：mAbs

authors： Marcucci F,Bellone M,Rumio C,Corti A

更新日期：2013-01-01 00:00:00

abstract：:Given the increasing use of combination therapy with multiple monoclonal antibodies (mAbs), there is a clinical need for multiplexing assays. For the frequently co-administered anti-human epidermal growth factor receptor 2 (HER2) mAbs trastuzumab and pertuzumab, we developed a high-throughput and robust hybrid ligand-...

journal_title：mAbs

authors： Schokker S,Fusetti F,Bonardi F,Molenaar RJ,Mathôt RAA,van Laarhoven HWM

更新日期：2020-01-01 00:00:00

abstract：:During cell line development for an IgG1 antibody candidate (mAb1), a C-terminal extension was identified in 2 product candidate clones expressed in CHO-K1 cell line. The extension was initially observed as the presence of anomalous new peaks in these clones after analysis by cation exchange chromatography (CEX-HPLC) ...

journal_title：mAbs

authors： Scott RA,Rogers R,Balland A,Brady LJ

更新日期：2014-01-01 00:00:00

abstract：:The development of antibody therapeutics relies on animal models that accurately recapitulate disease biology. Syngeneic mouse models are increasingly used with new molecules to capture the biology of complex cancers and disease states, and to provide insight into the role of the immune system. The establishment of sy...

journal_title：mAbs

authors： Wang F,Tsai JC,Davis JH,Chau B,Dong J,West SM,Hogan JM,Wheeler ML,Bee C,Morishige W,Cayton T,David-Brown D,Zhang C,Kozhich A,Sproul T,Dollinger G,Rajpal A,Strop P

更新日期：2020-01-01 00:00:00

abstract：:Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy o...

journal_title：mAbs

authors： Larios Mora A,Detalle L,Gallup JM,Van Geelen A,Stohr T,Duprez L,Ackermann MR

更新日期：2018-07-01 00:00:00

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：: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：: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：:Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other t...

journal_title：mAbs

authors： Yang X,Xu W,Dukleska S,Benchaar S,Mengisen S,Antochshuk V,Cheung J,Mann L,Babadjanova Z,Rowand J,Gunawan R,McCampbell A,Beaumont M,Meininger D,Richardson D,Ambrogelly A

更新日期：2013-09-01 00:00:00

abstract：:CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the ...

journal_title：mAbs

authors： Gowda A,Ramanunni A,Cheney C,Rozewski D,Kindsvogel W,Lehman A,Jarjoura D,Caligiuri M,Byrd JC,Muthusamy N

更新日期：2010-01-01 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：:Bispecific antibodies can uniquely influence cellular responses, but selecting target combinations for optimal functional activity remains challenging. Here we describe a high-throughput, combinatorial, phenotypic screening approach using a new bispecific antibody target discovery format, allowing screening of hundred...

journal_title：mAbs

authors： Bhatta P,Whale KD,Sawtell AK,Thompson CL,Rapecki SE,Cook DA,Twomey BM,Mennecozzi M,Starkie LE,Barry EMC,Peters SJ,Kamal AM,Finney HM

更新日期：2021-01-01 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：: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

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：: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：: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：: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：:An immunotoxin (IT) constructed with RFB4, a murine anti-CD22 monoclonal antibody, and the "deglycosylated" A chain of ricin has shown activity at safe doses in patients with non-Hodgkin lymphoma and in children with acute lymphoblastic leukemia. The dose limiting toxicity is vascular leak syndrome (VLS), which appear...

journal_title：mAbs

authors： Liu XY,Pop LM,Schindler J,Vitetta ES

更新日期：2012-01-01 00:00:00