Recent successes of T cell receptor based adoptive cell transfer therapy have generated new excitement about this therapeutic approach. However, lacking a high-throughput method of screening of naturally occurring high- affinity therapeutic T cell receptors (TCRs) has put a limit on how widely this approach can be applied to different kinds of cancers and a large range of patients. In this study, we propose to develop an integrated platform that on one hand drastically speeds up the identification and test of therapeutic TCRs and on the other hand, profiles common cancer antigens and HLAs expressed in tumor sample at single cell level. We name it Magic-HAT for Matching antigen identification in cancer with High-Affinity TCRs. The success of this project breaks the bottleneck of identifying and testing naturally occurring therapeutic high-affinity TCRs in adoptive cell transfer therapy setting for a large panel of cancer antigen epitopes. It enables a new capability on using combination of TCRs in TCR-redirected T cells for adoptive cell transfer therapy in cancer.
This project aims to an integrated technology for speeding up the process of therapeutic T cell receptor identification and validation. This is highly relevant to both highly mutated cancers as well as cancers with low mutation burden. The success of this project will make it possible to test combinatorial T cell receptor re-directed adoptive cell transfer therapy in animal models and future clinical trials. Expected results not only establish the foundation for a paradigm shift for future cancer immune therapy, but also make T cell receptor based adoptive cell transfer therapy available to more patients.
