TY - JOUR AU - Walsh, Scott R. AU - Simovic, Boris AU - Chen, Lan AU - Bastin, Donald AU - Nguyen, Andrew AU - Stephenson, Kyle AU - Mandur, Talveer S. AU - Bramson, Jonathan L. AU - Lichty, Brian D. AU - Wan, Yonghong T1 - Endogenous T cells prevent tumor immune escape following adoptive T cell therapy PY - 2019/12/02/ AB - While the outcome of adoptive T cell therapy (ACT) is typically correlated with the functionality of the inoculated T cells, the role of the endogenous T cells is unknown. The success of checkpoint blockade therapy has demonstrated the potentially curative value of preexisting tumor-primed T cells in cancer treatment. Given the results from checkpoint blockade therapy, we hypothesized that endogenous T cells contribute to long-term survival following ACT. Here, we describe a therapeutic approach combining ACT with an oncolytic vaccine that allows simultaneous analysis of antitumor immunity mediated by transferred and endogenous T cells. We found that, in addition to promoting the expansion and tumor infiltration of the transferred T cells, oncolytic vaccines boosted tumor-primed host T cells. We determined that transferred T cells contributed to rapid destruction of large tumor masses while endogenous T cells concurrently prevented the emergence of antigen-loss variants. Moreover, while transferred T cells disappeared shortly after tumor regression, endogenous T cells secured long-term memory with a broad repertoire of antigen specificity. Our findings suggest that this combination strategy may exploit the full potential of ACT and tumor-primed host T cells to eliminate the primary tumor, prevent immune escape, and provide long-term protective memory. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI126199 VL - 129 IS - 12 UR - https://doi.org/10.1172/JCI126199 SP - 5400 EP - 5410 PB - The American Society for Clinical Investigation ER -