Parker Bridge Fellows Program; Funded in partnership between Parker Institute for Cancer Immunotherapy and the V Foundation
Cancer immunotherapy holds great promise to treat cancers since it boosts the human body’s own immune system to eradicate cancers. Cytotoxic T cells are the central arsenal in our immune system to find and attack cancer cells without harming the healthy cells. These T cells harbor a high diversity of T cell receptors (TCR) to specifically recognize tumor neoantigens, which are proteins arising from mutations in cancers but not in normal cells. Neoantigens are highly unique in each patient. Therefore, it is essential to identify tumor neoantigens and paired TCRs in each patient to develop personalized cancer immunotherapies such as tumor neoantigen vaccines and TCR-engineered T cell adoptive therapy. Here we will develop an innovative platform to map neoantigen specificity, TCR repertoire and molecular phenotype of T cells at the single-cell level. This platform will permit a rapid, low-cost, and high-throughput mapping of patient-specific neoantigens, allowing cancer immunotherapy more accessible to each patient. Linking TCR recognition of tumor neoantigens with molecular programming of tumor-targeting T cells, we will understand how the T cells “see” neoantigens impact their cell fate decision to become highly-protective T cells that eliminate cancers or exhausted T cells that cannot work. Completion of this work will significantly facilitate the development of patient-tailored cancer immunotherapy.