Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan.

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：: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：:Biological therapies have revolutionized the treatment of several cancers and systemic immune-mediated inflammatory conditions. Expiry of patents protecting a number of biologics has provided the opportunity to commercialize highly similar versions, known as biosimilars. Biosimilars are approved by regulatory agencies...

journal_title：mAbs

authors： Scheinberg M,Pineda C,Castañeda-Hernández G,Zarbá JJ,Damião A,Arantes LH Jr,Jacobs I

更新日期：2018-08-01 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：: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

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：:Therapeutic monoclonal antibodies (mAbs) are highly complex proteins that must be exhaustively characterized according to the regulatory authorities' recommendations. MAbs display micro-heterogeneity mainly due to their post-translational modifications, but also to their susceptibility to chemical and physical degrada...

journal_title：mAbs

authors： Rouby G,Tran NT,Leblanc Y,Taverna M,Bihoreau N

更新日期：2020-01-01 00:00:00

abstract：:Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched ...

journal_title：mAbs

authors： Munro TP,Mahler SM,Huang EP,Chin DY,Gray PP

更新日期：2011-09-01 00:00:00

abstract：:A costimulatory signal is required for the full activation of T cells, in addition to the antigen-specific signal via the T cell receptor. The inducible costimulator, ICOS is one of the costimulatory molecules that play an essential role in this process, particularly in the expansion or the development of effector T c...

journal_title：mAbs

authors： Maeda M,Ito Y,Hatanaka T,Hashiguchi S,Torikai M,Nakashima T,Sugimura K

更新日期：2009-09-01 00:00:00

abstract：:Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque path...

journal_title：mAbs

authors： Gouras GK

更新日期：2009-03-01 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：: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：: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：: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：: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：:Genomic studies have been revolutionized by the use of next generation sequencing (NGS) that delivers huge amounts of sequence information in a short span of time. The number of applications for NGS is rapidly expanding and significantly transforming many areas of life sciences. The field of antibody research and disc...

journal_title：mAbs

authors： Fischer N

更新日期：2011-01-01 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：: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 Fc glycosylation of therapeutic antibodies is crucial for their effector functions and their behavior in pharmacokinetics and pharmacodynamics. To monitor the Fc glycosylation in bioprocess development and characterization,high-throughput techniques for glycosylation analysis are needed. Here, we describe the deve...

journal_title：mAbs

authors： Reusch D,Haberger M,Kailich T,Heidenreich AK,Kampe M,Bulau P,Wuhrer M

更新日期：2014-01-01 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：:Gel microdroplet - fluorescence activated cell sorting (GMD-FACS) is an innovative high throughput screening platform for recombinant protein libraries, and we show here that GMD-FACS can overcome many of the limitations associated with conventional screening methods for antibody libraries. For example, phage and cell...

journal_title：mAbs

authors： Fang Y,Chu TH,Ackerman ME,Griswold KE

更新日期：2017-11-01 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：: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：:The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory r...

journal_title：mAbs

authors： Richter F,Seifert O,Herrmann A,Pfizenmaier K,Kontermann RE

更新日期：2019-05-01 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：: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：: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：: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：: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