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- Title
Endogenous T cells prevent tumor immune escape following adoptive T cell therapy.
- Authors
Walsh, Scott R.; Simovic, Boris; Lan Chen; Bastin, Donald; Nguyen, Andrew; Stephenson, Kyle; Mandur, Talveer S.; Bramson, Jonathan L.; Lichty, Brian D.; Yonghong Wan; Chen, Lan; Wan, Yonghong
- Abstract
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.
- Subjects
T cells; CELLULAR therapy; CELL tumors; LONG-term memory; CANCER cells; TUMOR treatment; ANIMAL experimentation; CELL lines; COMPARATIVE studies; IMMUNITY; IMMUNIZATION; RESEARCH methodology; MEDICAL cooperation; MICE; RESEARCH; TUMORS; CANCER vaccines; EVALUATION research
- Publication
Journal of Clinical Investigation, 2019, Vol 129, Issue 12, p5400
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI126199