Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells

Autor: Osamu Sato, Takahiro Tsuchikawa, Takuma Kato, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Yuta Takeuchi, Katsunori Sasaki, Toru Nakamura, Kazufumi Umemoto, Tomohiro Suzuki, Linan Wang, Yizheng Wang, Kanako C. Hatanaka, Tomoko Mitsuhashi, Yutaka Hatanaka, Hiroshi Shiku, Satoshi Hirano
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cancers, Vol 15, Iss 3, p 601 (2023)
Druh dokumentu: article
ISSN: 15030601
2072-6694
DOI: 10.3390/cancers15030601
Popis: Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.
Databáze: Directory of Open Access Journals
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