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

Sato, Osamu; Tsuchikawa, Takahiro; Kato, Takuma et al.

Cancers, 2023, 15(3), 601

Permalink : https://hdl.handle.net/2115/88802

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https://doi.org/10.3390/cancers15030601     1

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アクセス権
metadata only access
URI
https://hdl.handle.net/2115/88802
タイトル
Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells
著者
Sato, Osamu ; Tsuchikawa, Takahiro ; Kato, Takuma ; Amaishi, Yasunori ; Okamoto, Sachiko ; Mineno, Junichi ; Takeuchi, Yuta ; Sasaki, Katsunori ; Nakamura, Toru ; Umemoto, Kazufumi ; Suzuki, Tomohiro ; Wang, Linan ; Wang, Yizheng ; Hatanaka, Kanako C. ; Mitsuhashi, Tomoko ; Hatanaka, Yutaka ; Shiku, Hiroshi ; Hirano, Satoshi
著者名
Sato, Osamu
e-Rad_Researcher
50507572
著者名
Tsuchikawa, Takahiro
著者名
Kato, Takuma
著者名
Amaishi, Yasunori
著者名
Okamoto, Sachiko
著者名
Mineno, Junichi
著者名
Takeuchi, Yuta
著者名
Sasaki, Katsunori
著者名
Nakamura, Toru
著者名
Umemoto, Kazufumi
著者名
Suzuki, Tomohiro
著者名
Wang, Linan
著者名
Wang, Yizheng
著者名
Hatanaka, Kanako C.
著者名
Mitsuhashi, Tomoko
著者名
Hatanaka, Yutaka
著者名
Shiku, Hiroshi
e-Rad_Researcher
50322813
著者名
Hirano, Satoshi
言語
英語
キーワード
chimeric antigen receptor engineered T cell
carcinoembryonic antigen
pancreatic ductal carcinoma
adoptive cell therapy
orthotopic xenograft mouse model
発行日
2023-02
出版者
MDPI
収録物名
Cancers
巻(号)
15(3)
ページ
601
抄録
Simple Summary Pancreatic ductal adenocarcinoma is one of the most lethal malignancies, and there are vast unmet medical needs. In this study, we hypothesized that chimeric antigen receptor engineered T cell (CAR-T) targeting carcinoembryonic antigen (CEA) would be effective in the treatment of pancreatic ductal adenocarcinoma. In vivo experiments in a more clinically similar environment were considered necessary; we examined the antitumor effects of adoptive anti-CEA-CAR-T, using orthotopic xenograft mouse models of pancreatic ductal adenocarcinoma. As result, the therapeutic effect of anti-CEA-CAR-T therapy was related to the CEA expression level. Furthermore, the retrospective analysis of pathological findings from pancreatic ductal adenocarcinoma patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. These findings show that anti-CEA-CAR-T therapy can be useful for pancreatic ductal adenocarcinoma; furthermore, the pathological findings of CEA can be clinically used as biomarkers to select cases for anti-CEA-CAR-T therapy. 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.
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学術雑誌論文
出版タイプ
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出版社版DOI
https://doi.org/10.3390/cancers15030601