Please join the AAPS Bioanalytical Community on July 23rd @ noon EDT for an Open Scientific Discussion:
The MHC Associated Peptide Proteomics (MAPPs) Assays in the Immunogenicity Risk Assessment of Therapeutic Proteins and Novel Modalities.
Immunogenicity is an essential consideration during the development and licensure of any therapeutic protein because it affects the safety and/or efficacy of the product. In vitro assays that measure T cells response against a protein therapeutic can be useful when selecting a drug candidate from among alternatives. Major Histocompatibility Complex (MHC) Associated Peptide Proteomics (MAPPs) is a unique assay that in principle can identify peptides derived from the therapeutic protein that are associated with an individual subject's MHC variants. Here, specific examples of the application of MAPPs in assessing the immunogenicity of protein therapeutics are provided. These include: (i) Comparing recombinant Factor VIIa (FVIIa) and its engineered variant Vatreptacog Alfa (VA) which has only 3 amino acid substitutions. This is a useful model system because while FVIIa used therapeutically rarely elicit an immune response, 11% of patients treated with VA in a clinical trial developed anti-drug antibodies. (ii) Use of the MAPPs assay to provide a mechanistic explanation for clinical observations that plasma derived FVIII products are less immunogenic than recombinant products. (iii) MAPPs assays in the context of novel modalities. Most MAPPs workflows have been designed to identify protein derived peptides presented on MHC-II. Many novel modalities (Gene Therapy, CRISPR-Cas) rely on intracellular protein production following intracellular gene expression. This involves presentation of protein derived on MHC Class I (MHC-I) proteins. Descriptions of the different workflows for identifying peptides associated with class 1 and class 2 MHC molecules will be described.
The presentation provides a current overview of the use of MAPPs in immunogenicity assessments.
Presenter: Zuben Sauna (Director, Division of Hemostasis, FDA)
Moderator: Sanjeev Bhardwaj (Moderna Therapeutics)
Have an idea for an upcoming session?
Please contact the OSD Committee Co-Chairs, @Sanjeev Bhardwaj & @Laurelle Calliste
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#bioanalysis #Bioanalytical #OSD #OpenScientificDiscussions
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Sanjeev Bhardwaj
Moderna Therapeutics
Cambridge, MA.
[email protected]Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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