期刊
CLINICAL CANCER RESEARCH
卷 27, 期 5, 页码 1538-1552出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-19-2163
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类别
资金
- Pancreatic Cancer UK Grand Challenge award
- Pancreatic Cancer Research Fund
- Canary Foundation of British Columbia Cancer Foundation
- Cancer Research UK [C16420/A18066]
By investigating CEACAM7 as a potential therapeutic target for PDAC, researchers have developed CEACAM7-targeting CAR T cells that demonstrate efficacy in targeting antigen-expressing tumor cells and inducing remission in patient-derived xenograft tumors.
Purpose: To investigate whether CEACAM7 represents a novel therapeutic target for treating pancreatic ductal adenocarcinoma (PDAC) and to generate CEACAM7-targeting CAR T cells to test this hypothesis. Experimental Design: We identified CEACAM7 (CGM2), a member of the CEA family of proteins with expression restricted to the colon and pancreas, as a potential CAR T-cell target for PDAC. We probed a panel of PDAC tumor sections as well as patient-derived PDAC cell cultures for CEACAM7 expression. We generated CAR-targeting CEACAM7, and assessed antitumor efficacy of CEACAM7 CAR T cells using in vitro and in vivo models. Results: We show here that CEACAM7 is expressed in a large subset of PDAC tumors, with low to undetectable expression in all normal tissues tested. CEACAM7 is also expressed in primary PDAC cultures isolated from patient-derived tumors, with high expression within the cancer stem cell-enriched subset. CAR T cells targeting CEACAM7 are capable of targeting antigen-expressing tumor cells, and mediate remission in patient-derived xenograft tumors. Conclusions: We identify CEACAM7 as a potential therapeutic target in PDAC and describe the development of CEACAM7-targeted CAR T cells with efficacy against PDAC.
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