Journal
CANCER CELL
Volume 35, Issue 2, Pages 221-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.01.002
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Funding
- University Cancer Research Fund at the University of North Carolina at Chapel Hill, United States
- National Cancer Institute, United States [R01-CA193140-03, R03CA223886]
- Rivkin Center for Ovarian Cancer, United States
- Department of Defense, United States [W81XWH-16-1-0501, W81XWH-16-1-0500]
- National Institute of Dental & Craniofacial Reseacrh, United States [R01DE028172]
- National Cancer Institute Center Core support grant, United States [5P30CA016086-41]
- National Cancer Institute Cancer core grant, United States [P30-CA016086-40]
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The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. We also found that 4-1BB co-stimulation promotes lower PD-1 expression in B7-H3.CAR-Ts, and superior antitumor activity when targeting tumor cells that constitutively expressed PD-L1. We took advantage of the cross-reactivity of the B7-H3.CAR with murine B7-H3, and found that B7-H3.CAR-Ts significantly controlled tumor growth in a syngeneic tumor model without evident toxicity. These findings support the clinical development of B7-H3.CAR-Ts.
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