Utilizing dual-specific CD4+ T cells in combination with oncolytic virotherapy for treatment of cancer (P2118)

Abstract Engineering T cell specificity to direct them against tumor cells utilizing chimeric antigen receptors (CARs) has emerged as an exciting technique for adoptive T cell therapy. The effectiveness of adoptive transfer therapies can be limited by a number of factors, including ability of T cells to engraft, the degree to which they infiltrate the tumor, and the immunosuppressive nature of the tumor. Oncolytic viruses (OVs) are capable of overcoming these limitations, and can serve as effective booster vaccines. In an effort to capitalize on these features, we have generated dual-specific T cells that bear TCRs specific for the OV, and CARs specific for the tumor. Using murine tumor models, we have observed significant boosting capacity of adoptively transferred dual-specific CD4+ or CD8+ T cells to tumor-bearing hosts in response to infusion with OV. Boosting with OV also dramatically influenced the distribution of the CAR-T cells, driving the cells to proliferate throughout the body. We now seek to examine the utility of dual-specific CD4+ T cells in adoptive transfer therapies. We have found that CAR-engineered CD4+ T cells are capable of mediating anti-tumor immunity, and are investigating the combination of these cells with OV to further enhance their anti-tumor efficacy. Given the promising clinical outcomes of both CAR T cells and OVs, we believe our combinatorial approach will provide a clinically feasable strategy to maximize the therapeutic potential of both therapies.