Technologies for personalizing cancer immunotherapies

Abstract

At the heart of most cancer immunotherapies are the specific interactions between tumor-infiltrating T cells, and the antigens that attract those T cells into the tumor. It has become increasingly apparent that (mutation containing) neoantigens likely play an important role in this regard. Putative neoantigens are identified by tumor exome analysis, but finding which of those candidates actually promote T cell tumor infiltration is challenging, as is pairing such antigens with the cognate T cell receptor (TCR) genes. Technologies that can address this challenge can help pave the way for personalized immunotherapies. For example, the active neoantigens can be engineered into personalized cell-based cancer vaccines, while the cognate TCRs represent engineered T cell therapy opportunities. I will discuss a nanotech/microchip tool that we have recently developed to address this challenge. The platform allows for the non-destructive enumeration of neoantigen specific T cell populations from either tumor infiltrating lymphocytes (TILs) or unexpanded peripheral blood mononuclear cells (PBMCs), beginning with as few as 10,000 CD8+ cells. I will discuss the application of the platform for kinetic studies of patient responses to checkpoint inhibitor therapy (via blood analysis), as well as applications for matching neoantigen-specificity with T cell receptor genes. I will also discuss how the resultant data can be used to guide the refinement of neoantigen prediction algorithms.

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