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Chimeric Antigen Receptor T Cell Therapy Targeting ICAM-1 in Gastric Cancer

Authors
 Minkyu Jung  ;  Yanping Yang  ;  Jaclyn E McCloskey  ;  Marjan Zaman  ;  Yogindra Vedvyas  ;  Xianglan Zhang  ;  Dessislava Stefanova  ;  Katherine D Gray  ;  Irene M Min  ;  Raza Zarnegar  ;  Yoon Young Choi  ;  Jae-Ho Cheong  ;  Sung Hoon Noh  ;  Sun Young Rha  ;  Hyun Cheol Chung  ;  Moonsoo M Jin 
Citation
 MOLECULAR THERAPY-ONCOLYTICS, Vol.18 : 587-601, 2020-08 
Journal Title
MOLECULAR THERAPY-ONCOLYTICS
Issue Date
2020-08
Keywords
Chimeric antigen receptor ; Gastric cancer ; T cell imaging ; inducible cytokines
Abstract
Cancer therapy utilizing adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated remarkable clinical outcomes in hematologic malignancies. However, CAR T cell application to solid tumors has had limited success, partly due to the lack of tumor-specific antigens and an immune-suppressive tumor microenvironment. From the tumor tissues of gastric cancer patients, we found that intercellular adhesion molecule 1 (ICAM-1) expression is significantly associated with advanced stage and shorter survival. In this study, we report a proof-of-concept study using ICAM-1-targeting CAR T cells against gastric cancer. The efficacy of ICAM-1 CAR T cells showed a significant correlation with the level of ICAM-1 expression in target cells in vitro. In animal models of human gastric cancer, ICAM-1-targeting CAR T cells potently eliminated tumors that developed in the lungs, while their efficacy was more limited against the tumors in the peritoneum. To augment CAR T cell activity against intraperitoneal tumors, combinations with paclitaxel or CAR activation-dependent interleukin (IL)-12 release were explored and found to significantly increase anti-tumor activity and survival benefit. Collectively, ICAM-1-targeting CAR T cells alone or in combination with chemotherapy represent a promising strategy to treat patients with ICAM-1+ advanced gastric cancer.
Files in This Item:
T202006751.pdf Download
DOI
10.1016/j.omto.2020.08.009
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Choi, Yoon Young(최윤영) ORCID logo https://orcid.org/0000-0002-2179-7851
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182730
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