Journal
CELL REPORTS
Volume 23, Issue 7, Pages 2130-2141Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.04.051
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Funding
- NIH [R01CA138738-05, P01CA059350, P01CA190174-03, P01CA23766, P50 CA192937-02, R01CA55349, P01CA00878, DP5OD023056]
- Annual Terry Fox Run for Cancer Research (New York, NY)
- Carson Family Charitable Trust
- William Lawrence and Blanche Hughes Foundation
- Emerald Foundation
- Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center
- Lymphoma Foundation
- Leukemia and Lymphoma Society
- Jake Wetchler Foundation
- Memorial Sloan Kettering (T32 Investigational Therapeutics Training Program Grant) [5T32-CA009207-38]
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Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy.
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