Micro-and Nanotechnologies for Personalizing Cancer Immunotherapy
James R. Heath
Caltech Division of Chemistry and Chemical Engineering, Pasadena, CA, USA
At the heart of most cancer immunotherapies are the specific interactions between the principle cancer cell killers, T cells, and antigens presented by the tumor cells.Those interactions may be exposed through the use of checkpoint inhibitors, or they can be amplified through the use of engineered cell-based therapies.We are particularly concerned with Class I MHC (mutated) neoantigen-CD8+ T cell recognition.In principle, neoantigens that draw T cells into a tumor can comprise personalized vaccines, and the T cell receptors (TCRs) that recognize those neoantigens can be engineered as personalized cellular therapies.I will discuss our approach, called nanoparticle-barcoded nucleic acid cell sorting (NP-barcoded NACS), designed for enumerating neoantigen-specific T cell populations from non-expanded tumor infiltrates or peripheral blood, and for pairing those neoantigen-specific CD8+ T cell populations with the cognate TCRa/b gene, using single cell sequencing methods.Analysis of cancer patient materials representing multiple tumor types will be presented.A major goal of this work is to provide experimental and theoretical guidance for improving neoantigen prediction algorithms.As a complement to this experimental program, I will also discuss quantum mechanical and molecular dynamics calculations intended to assess the energetic and kinetic landscape of neoantigen/MHC interactions.Those calculations, which are only now becoming possible using modern computational resources, are intended to provide a detailed physico-chemical foundation of the more standard statistical-based computational methods predicting antigen/MHC binding.
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