Utilizing CD39 and CD103 to identify tumor-reactive TCRs and transducing them into T cells with no tumor reactivity leads to tumor killing in-vitro 9326

Abstract Description CD8+ tumor infiltrating lymphocytes (TIL) positive for CD39 and CD103 are enriched for tumor reactivity/killing, while TIL derived from tumors that are negative for CD39 and CD103 (double negative, DN) have low specificity/killing for autologous tumor. Sorting TIL for CD39 and CD103 and expanding this sub-population leads to a cell therapy drug product with a high degree of tumor specificity. Here we show a process where we sequenced the TCRs of a DP TIL population, selected a highly clonal TCR, and transduced this TCR into allogenic PBMCs or syngeneic DN cells. This transduction protocol led to potent tumor reactivity in vitro. Utilizing the DP TIL specificity to narrow the pool of tumor-specific TCRs will enable us to rapidly identify top TCR candidates for individualized patient therapies. This technology may also be useful in discovering TCRs that could be off-the-shelf agents to treat multiple tumor types across a specific HLA allele (e.g. HPV-specific targets or driver mutations etc…). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)