Preclinical Development – Biomolecular
2019 PharmSci 360
Prediction of effective neoantigen targets requires consideration of multiple cellular and immunological pathways. Early and critical steps in generating an antigen-specific cell mediated immune response includes effective intracellular antigen processing and presentation of an antigenic sequence on surface MHC molecules. In silico predictive tools provide high-throughput analysis of peptide-MHC II binding but cannot predict intracellular processing which may affect presentation of antigenic sequences. In vitro antigen presentation assays pose limitations in being time consuming, labor intensive, restricted by donor cell quantity and complicated by HLA-DR allelic diversity. To address these weaknesses, we have proposed a competition based high-throughput in vitro assay for analysis of intracellular neoantigen processing and presentation using mono-allelic MHC class II antigen presenting cell lines. Utilization of high-throughput cell-based assays for neoantigen prediction will allow for efficient screening of target candidates at early critical stages in the development of antigen specific immunity.