Matthew Baker
Babraham Institute
Peripheral blood mononuclear cellMolecular biologyVirologyAntibodyChemistryEpitopeIn vitroImmunologyEx vivoIn silicoT cellImmunogenicityProtein therapeuticsDeimmunizationPharmacology toxicologyMonoclonal antibodyComputational biologyMedicineBiologyImmune system
Publications 25
#1Neha N. Pardeshi (Anschutz Medical Campus)H-Index: 4
#2M AhmadiH-Index: 7
Last. John F. Carpenter (Anschutz Medical Campus)H-Index: 106
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ABSTRACT Among patients that receive Remicade® therapy, more than 20% have adverse infusion related reactions and approximately 50% have immunogenic responses. 1 , 2 , 3 Upon characterization of initial Remicade®-IV solution we observed a high concentration of subvisible particles that could inadvertently be delivered to patients. This solution was processed through the IV infusion system, mimicking the typical clinical administration setup - either with or without an in-line filter connected to...
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 and leading to inhibition of protein synthesis. Peptide mapping using an ex vivo human T cell assay determined that ...
9 CitationsSource
#1Marisa K. Joubert (Amgen)H-Index: 12
#2Meghana Deshpande (Amgen)H-Index: 4
Last. Vibha Jawa (Amgen)H-Index: 19
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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 naive 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 a panel of secreted cytokines. The response in the assay to 10 monoclonal antibodies was found to be in agreement with the clinic...
59 CitationsSource
#1Carl I. Webster (MedImmune)H-Index: 19
Last. Matthew BakerH-Index: 18
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ABSTRACTThe immunogenicity of clinically administered antibodies has clinical implications for the patients receiving them, ranging from mild consequences, such as increased clearance of the drug from the circulation, to life-threatening effects. The emergence of methods to engineer variable regions resulting in the generation of humanised and fully human antibodies as therapeutics has reduced the potential for adverse immunogenicity. However, due to differences in sequence referred to as alloty...
9 CitationsSource
#1Tim JonesH-Index: 8
Last. Matthew BakerH-Index: 18
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An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a –mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclona...
43 CitationsSource
#2Richard WeldonH-Index: 5
Last. Matthew BakerH-Index: 18
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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 current standard of treatment, the humanized monoclonal antibody alemtuzumab, is associated with the development of anti-drug antibodies in a high proportion of patients. In order to address this problem, we have identified a novel murine anti-CD52 antibody which has been humanize...
24 CitationsSource
#1M AhmadiH-Index: 7
#2Christine J. Bryson (University of Cambridge)H-Index: 5
Last. Mark H. FoggH-Index: 4
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Purpose Determine the effect of minute quantities of sub-visible aggregates on the in vitro immunogenicity of clinically relevant protein therapeutics.
95 CitationsSource
#1Vera Brinks (UU: Utrecht University)H-Index: 15
#2Daniel Weinbuch (LEI: Leiden University)H-Index: 6
Last. Wim Jiskoot (LEI: Leiden University)H-Index: 84
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All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to pre...
51 CitationsSource
#1Marisa K. Joubert (Amgen)H-Index: 12
#2Martha M. HokomH-Index: 12
Last. Vibha JawaH-Index: 19
view all 11 authors...
Abstract Aggregation of biotherapeutics has the potential to induce an immunogenic response. Here, we show that aggregated therapeutic antibodies, previously generated and determined to contain a variety of attributes (Joubert, M. K., Luo, Q., Nashed-Samuel, Y., Wypych, J., and Narhi, L. O. (2011) J. Biol. Chem. 286, 25118–25133), can enhance the in vitro innate immune response of a population of naive human peripheral blood mononuclear cells. This response depended on the aggregate type, inhere...
181 CitationsSource
#1Matthew BakerH-Index: 18
#2Helen M ReynoldsH-Index: 2
Last. Christine J. BrysonH-Index: 5
view all 4 authors...
The immunogenicity of protein therapeutics has so far proven to be difficult to predict in patients, with many biologics inducing undesirable immune responses that are directed towards the therapeutic resulting in reduced efficacy, anaphylaxis and occasionally life threatening autoimmunity. The most common effect of administrating an immunogenic protein therapeutic is the development of a high affinity anti-therapeutic antibody response. Furthermore, it is clear from clinical studies that protei...
220 CitationsSource