《生命科学》 2025, 37(4): 450-458
CAR-T细胞治疗胃癌的研究进展
摘 要：
嵌合抗原受体T 细胞(chimeric antigen receptor T cell, CAR-T) 是一种前沿的细胞免疫治疗方法，在血液系统恶性肿瘤的治疗中已经取得了一些突破，但是在胃癌的治疗中仍然面临诸多挑战，不过越来越多的临床试验开始尝试将CAR-T 用于胃癌的治疗。本文综述了CAR-T 细胞的发展历程，并探讨了其在胃癌治疗中的主要靶点，例如针对Claudin18.2 的CAR-T 细胞治疗已取得初步突破。同时，本文也概述了CAR-T 细胞治疗胃癌所面临的挑战及潜在应对策略，包括增强CAR-T 细胞的抗原特异性识别能力、提高其浸润效率、改善免疫抑制性微环境、逆转CAR-T 细胞耗竭以及联合溶瘤病毒等。最后，本文简要讨论了提升CAR-T 细胞治疗胃癌效果的途径，期望能通过不同的治疗策略为胃癌患者带来更多的治愈希望。
通讯作者：刘滨磊 , Email:liubl@hbut.edu.cn
Abstract:
Chimeric antigen receptor T-cell (CAR-T) therapy represents a revolutionary approach in adoptive immunotherapy, demonstrating remarkable efficacy against hematologic malignancies. Despite these advances, significant challenges persist in translating CAR-T efficacy to solid tumors, particularly in gastric cancer where emerging clinical trials are actively investigating CAR-T applications. This review systematically examines the developmental trajectory of CAR-T technology, focusing on current molecular targets for gastric cancer intervention with particular emphasis on Claudin 18.2-specific constructs that have shown promising preclinical outcomes. Additionally, the paper introduces the challenges faced in the application of CAR-T cell therapy for gastric cancer, along with potential solutions. These include enhancing CAR-T cells' antigen-specific recognition capabilities, augmenting their infiltration efficiency, modulating the immunosuppressive microenvironment to create a more favorable treatment landscape, reversing CAR-T cell exhaustion, and combining oncolytic virus, etc. Lastly, the paper briefly explores avenues to augment the efficacy of CAR-T cell therapy in gastric cancer, hoping to bring more hope for gastric cancer patients through different treatment strategies.
Communication Author：LIU Bin-Lei , Email:liubl@hbut.edu.cn
