SBIR Phase II: High throughput and antigen specific T-cell receptor discovery for solid tumor treatments

The broader impact of this Small Business Innovation (SBIR) Phase II project is to enable discovery of needed T-cell receptor (TCR) based therapeutics for late-stage cancer patients who have limited treatment options. These immunotherapies work by leveraging T-cells engineered with TCRs that will identify and destroy cancer cells that naturally present a target (antigen) specific to the cancer on their surface (e.g., cancer mutations). This project will apply a novel high-throughput platform developed in Phase I to screen millions of TCRs against a large set of cancer-related antigens to identify clinically relevant TCRs and validate the most promising TCRs for cancer-specific in-vitro and in-vivo killing. This project could impact society’s health by discovering TCRs that will serve as the basis for treatments against currently incurable cancers (e.g. breast cancer). The commercial impacts are potentially large. The total market size of T-cell therapeutics was $2.4 billion in 2018 and is estimated to reach $8.5 billion by 2027. The platform described by this proposal has the potential to discover many TCR based therapeutics, creating value for patients and society at large. The proposed project is to identify clinically valuable TCRs by applying a high-throughput TCR screening platform developed in Phase I. Data generated by this project could be critical for developing new immunotherapies against solid tumors and for understanding the biology that underlies TCR-antigen interaction. Screening millions of TCRs for functional activation against a large set of clinically relevant cancer antigens is challenging, as conventional screening technologies are largely limited to screening one antigen at a time. In contrast, the high-throughput screening assay developed in Phase I is capable of tracking interactions between hundreds of thousands of unique cells, where evidence linking TCR interaction with specific antigens that is captured and read out via single-cell sequencing. This project will generate data directly linking TCRs with 62 clinically important antigen targets. The most promising TCRs discovered will then be validated for specific and potent interaction against a target with in-vivo and in-vitro experiments. The objective of this project is to discover and validate a number of anti-cancer TCRs and generate pre-clinical data packages that illustrate their value as potential therapeutic drugs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.