Technologies for Personalizing Cancer Immunotherapies
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 molecular dynamics calculations intended to assess the energetic and kinetic landscape of neoantigen/MHC interactions. Those calculations are providing a detailed physico-chemical foundation for building statistical-based computational algorithms for predicting antigen/MHC binding.
Jim Heath is the Elizabeth Gilloon Professor and Professor of Chemistry at Caltech. He has directed the National Cancer Institute funded NSB Cancer Center since 2005, and he also co-Directs the UCLA Parker Institute for Cancer Immunotherapy. He received his Ph.D. from Rice University, and served on the research staff at IBM Watson before joining the faculty at UCLA in 1994, and then moving to Caltech in 2003. Heath’s group works on the development and application of single cell and molecular methods for fundamental cancer biology and translational oncology applications.