Despite multimodal treatment options, most gastrointestinal cancers are still associated with high mortality rates and poor responsiveness to immunotherapy. The unprecedented efficacy of chimeric antigen receptor (CAR)-engineered T cells in the treatment of haematological malignancies raised interest in translating CAR T cell therapies to the treatment of gastrointestinal cancers. Treatment of solid cancers with canonical CAR T cells faces substantial challenges, including the dense architecture of the tumour tissue, the tolerogenic environment with low tumour-intrinsic immunogenicity, the rareness of targetable tumour-selective antigens, the antigenic heterogeneity of cancer cells, and the profound metabolic and immune cell disbalances. This Review provides an overview of CAR T cell trials in the treatment of gastrointestinal cancers, discussing considerations relating to safety, efficacy, potential reasons for failure and options for improving CAR T cells for the future. In addition, lessons regarding how to improve efficacy are drawn from CAR T cells armed with adjuvants that sustain their activation within the hostile environment and activate resident immune cells. As the field is rapidly evolving, current treatment modalities and editing CAR T cell functionalities are being refined towards a potentially more successful CAR T cell therapy for gastrointestinal cancers.

© 2025. Springer Nature Limited.

尽管有多模式治疗选项，大多数胃肠道癌症仍然与高死亡率和对免疫疗法反应不佳相关。嵌合抗原受体（CAR）工程T细胞在血液系统恶性肿瘤治疗中的空前疗效引发了将CAR T细胞疗法应用于胃肠道癌症治疗的兴趣。使用经典CAR T细胞治疗实体瘤面临重大挑战，包括肿瘤组织的密集结构、具有低内在免疫原性的耐受性环境、可供靶向的选择性肿瘤抗原稀少、癌细胞的抗原异质性以及代谢和免疫细胞失衡严重等问题。本综述总结了CAR T细胞在胃肠道癌症治疗中的试验情况，讨论了安全性、疗效、可能失败的原因及未来改进CAR T细胞的方法。此外，还从携带佐剂的CAR T细胞中汲取经验，这些佐剂可以在恶劣环境中维持其激活状态并激活驻留免疫细胞。由于该领域正在迅速发展，目前的治疗方法和编辑CAR T细胞功能正在向着更成功的胃肠道癌症CAR T细胞治疗方向改进。

© 2025. Springer Nature Limited.