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

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

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)587-601
Number of pages15
JournalMolecular Therapy - Oncolytics
Volume18
DOIs
StatePublished - Sep 25 2020

Keywords

  • Chimeric antigen receptor
  • Gastric cancer
  • T cell imaging
  • inducible cytokines

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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