HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Hokkaido University Hospital >
Peer-reviewed Journal Articles, etc >

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

Files in This Item:

The file(s) associated with this item can be obtained from the following URL: https://doi.org/10.3390/cancers15030601


Title: Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells
Authors: Sato, Osamu Browse this author
Tsuchikawa, Takahiro Browse this author →KAKEN DB
Kato, Takuma Browse this author
Amaishi, Yasunori Browse this author
Okamoto, Sachiko Browse this author
Mineno, Junichi Browse this author
Takeuchi, Yuta Browse this author
Sasaki, Katsunori Browse this author
Nakamura, Toru Browse this author
Umemoto, Kazufumi Browse this author
Suzuki, Tomohiro Browse this author
Wang, Linan Browse this author
Wang, Yizheng Browse this author
Hatanaka, Kanako C. Browse this author
Mitsuhashi, Tomoko Browse this author
Hatanaka, Yutaka Browse this author
Shiku, Hiroshi Browse this author
Hirano, Satoshi Browse this author →KAKEN DB
Keywords: chimeric antigen receptor engineered T cell
carcinoembryonic antigen
pancreatic ductal carcinoma
adoptive cell therapy
orthotopic xenograft mouse model
Issue Date: Feb-2023
Publisher: MDPI
Journal Title: Cancers
Volume: 15
Issue: 3
Start Page: 601
Publisher DOI: 10.3390/cancers15030601
Abstract: 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.
Type: article
URI: http://hdl.handle.net/2115/88802
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 

 - Hokkaido University