©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Feb 24, 2026; 17(2): 114107
Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.114107
Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.114107
Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies
Chen Wang, Zi-Ke Chen, Yu-Gang Wang, Min Shi, Department of Gastroenterology, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Jin Zhang, Department of Traditional Medicine, Kongjiang Community Health Service Center, Shanghai 200082, China
Co-first authors: Chen Wang and Jin Zhang.
Co-corresponding authors: Yu-Gang Wang and Min Shi.
Author contributions: Wang C and Zhang J were the primary contributors to the manuscript writing and they contributed equally to this manuscript as co-first authors; Chen ZK revised the manuscript; Wang YG and Shi M conceptualized the theme and structure of this manuscript and they contributed equally to this manuscript as co-corresponding authors. All authors have read and approved the final manuscript.
Supported by Pujiang Project of Shanghai Magnolia Talent Plan, No. 24PJD098; Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality, No. 23ZR1458300; and Key Discipline Project of Shanghai Municipal Health System, No. 2024ZDXK0004.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Min Shi, MD, Chief Physician, Professor, Department of Gastroen
Received: September 11, 2025
Revised: October 23, 2025
Accepted: December 25, 2025
Published online: February 24, 2026
Processing time: 147 Days and 23.4 Hours
Revised: October 23, 2025
Accepted: December 25, 2025
Published online: February 24, 2026
Processing time: 147 Days and 23.4 Hours
Core Tip
Core Tip: Chimeric antigen receptor T cell therapy (CAR) has achieved remarkable success in hematologic cancers but faces unique barriers in solid tumors of the digestive system. This article highlights recent progress in optimizing antigen selection, CAR engineering, and delivery strategies, while discussing tumor-specific targets and clinical trials in gastric, colorectal, esophageal, hepatic, and pancreatic cancers. By addressing challenges such as the tumor microenvironment and therapeutic resistance, we provide perspectives on advancing CAR T cell therapy immunotherapy toward safe, effective, and durable treatments for gastrointestinal malignancies.