Modulation of drug-linker design to enhance in vivo potency of homogeneous antibody-drug conjugates;
Antibody-drug conjugates (ADCs) are a promising class of anticancer agents which have undergone substantial development over the past decade and are now achieving clinical success. The development of novel site-specific conjugation technologies enables the systematic study of architectural features within the antibody conjugated drug linker that may affect overall therapeutic indices. Here we describe the results of a systematic study […]... Read more
A deimmunised form of the ribotoxin, α-sarcin, lacking CD4+ T cell epitopes and its use as an immunotoxin warhead
Fungal ribotoxins that block protein synthesis can be useful warheads in the context of a targeted immunotoxin. α-Sarcin is a small (17 kDa) fungal ribonuclease produced by Aspergillus giganteus that functions by catalytically cleaving a single phosphodiester bond in the sarcin–ricin loop of the large ribosomal subunit, thus making the ribosome unrecognisable to elongation factors […]... Read more
Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
An In Vitro Comparative Immunogenicity Assessment (IVCIA) assay was evaluated as a tool for predicting the potential relative immunogenicity of biotherapeutic attributes. Peripheral blood mononuclear cells from up to 50 healthy naïve human donors were monitored up to 8 days for T-cell proliferation, the number of IL-2 or IFN-γ secreting cells, and the concentration of […]... Read more
Building a biologics capabilities network
This article explains how Abzena is building a biologics capabilities network through a slew of acquisitions. GEN May 15, 2016 (Vol. 36 No.10) http://www.genengnews.com/gen-articles/building-a-biologics-capabilities-network/5764/... Read more
The INNs and outs of antibody nonproprietary names
http://www.tandfonline.com/doi/full/10.1080/19420862.2015.1114320 Tim D. Jones, Paul J. Carter, Andreas Plückthun, Max Vásquez, Robert G.E. Holgate, Isidro Hötzel, Andrew G. Popplewell, Paul W.H.I. Parren, Markus Enzelberger, Hendrik J. Rademaker, Michael R. Clark, David C. Lowe, Bassil I. Dahiyat, Victoria Smith, John M. Lambert, Herren Wu, Mary Reilly, John S. Haurum, Stefan Dübel, James S. Huston, Thomas, Schirrmann, Richard A.J. Janssen, Martin […]... Read more
A comparison of the ability of the human IgG1 allotypes G1m3 and G1m1,17 to stimulate T-cell responses from allotype matched and mismatched donors.
Carl I. Webster, Christine J. Bryson, Edward A. Cloake, Tim D. Jones, Mark J. Austin, Anette C. Karle, Sebastian Spindeldreher, David C. Lowe & Matthew P. Baker. mAbs, Volume 8, Issue 2, 2016 ABSTRACT The immunogenicity of clinically administered antibodies has clinical implications for the patients receiving them, ranging from mild consequences, such as increased clearance of […]... Read more
Characterisation of a novel anti-CD52 antibody with improved efficacy and reduced immunogenicity
Holgate RGE, Weldon R, Jones TD, Baker MP (2015) Characterisation of a Novel Anti-CD52 Antibody with Improved Efficacy and Reduced Immunogenicity. PLoS ONE 10(9): e0138123. doi:10.1371/journal.pone.0138123 Abstract Anti-CD52 therapy has been shown to be effective in the treatment of a number of B cell malignancies, hematopoietic disorders and autoimmune diseases (including rheumatoid arthritis and multiple sclerosis); however the […]... Read more
In vitro and in vivo evaluation of cysteine rebridged trastuzumab–MMAE antibody drug conjugates with defined drug-to-antibody ratios
Penny Bryant, Martin Pabst, George Badescu, Matthew Bird, William McDowell, Estera Jamieson, Julia Swierkosz, Kosma Jurlewicz, Rita Tommasi, Korinna Henseleit, XiaoBo Sheng, Nicolas Camper, Anais Manin, Katarzyna Kozakowska, Karolina Peciak, Emmanuelle Laurine, Ruslan Grygorash, Andrew Kyle, David Morris, Vimal Parekh, Amrita Abhilash, Ji-won Choi, Jeff Edwards, Mark Frigerio, Matthew P. Baker, and Antony Godwin Abstract […]... Read more
In Vitro and In Vivo Evaluation of Cysteine Rebridged Trastuzumab–MMAE Antibody Drug Conjugates with Defined Drug-to-Antibody Ratios
The conjugation of monomethyl auristatin E (MMAE) to trastuzumab using a reduction bis-alkylation approach that is capable of rebridging reduced (native) antibody interchain disulfide bonds has been previously shown to produce a homogeneous and stable conjugate with a drug-to-antibody ratio (DAR) of 4 as the major product. Here, we further investigate the potency of the […]... Read more
Small Amounts of Sub-Visible Aggregates Enhance the Immunogenic Potential of Monoclonal Antibody Therapeutics
Maryam Ahmadi, Christine J. Bryson, Edward A. Cloake, Katie Welch, Vasco Filipe, Stefan Romeijn, Andrea Hawe, Wim Jiskoot, Matthew P. Baker, Mark H. Fogg. Pharmaceutical Research, An Official Journal of the American Association of Pharmaceutical Scientists, ISSN 0724-8741, Pharm Res, DOI 10.1007/s11095-014-1541-x Abstract PURPOSE: Determine the effect of minute quantities of sub-visible aggregates on the in vitro immunogenicity of clinically […]... Read more