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CAR-T 细胞疗法在实体瘤中的挑战与展望:来自胃癌的启示

英文原题:Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.

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Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.

PubMed 2025/07/04(内容时间) Br J Cancer Q1 · IF 7.8(JCR 2025)

研究概要

胃癌(GC)仍然是一项重大挑战,因为它是全球最常见且最致命的恶性肿瘤之一。

中文摘要

胃癌(GC)仍然是全球最常见和致死率最高的恶性肿瘤之一,构成重大挑战。由于其复杂性,表现为多种组织学亚型和基因突变,其管理和治疗仍然是一项巨大挑战。近年来手术、化疗和放疗的进展仅略微改善了晚期GC的预后,凸显了创新治疗策略的迫切需求。嵌合抗原受体(CAR)T细胞疗法已成为血液系统恶性肿瘤的突破性疗法,目前正在研究作为实体瘤的潜在治疗方法。CAR-T在GC中的显著疗效已在临床前和临床研究中得到证实。GC治疗的潜在生物标志物包括CLDN18.2、MSLN、CEA、EpCAM、MUC1、HER2、FOLR1和NKG2DL。然而,应用针对GC的CAR-T细胞仍面临相当大的挑战。新型CAR设计有望通过促进T细胞浸润、增强T细胞持久性、降低靶向非肿瘤毒性、提高对免疫抑制性肿瘤微环境(TME)的耐受性以及加强与异质性抗原的相互作用,来增强CAR-T细胞疗法对GC的疗效。本综述总结了CAR-T细胞疗法治疗GC的相关临床前研究和临床进展,评估其治疗潜力和安全性,讨论当前挑战,并概述临床转化的未来方向。

展开英文摘要原文

Gastric cancer (GC) remains a significant challenge as it is one of the most prevalent and lethal malignancies worldwide. Due to its complexity characterised by diverse histological subtypes and genetic mutations, its management and treatment remain a substantial challenge. Recent advancements in surgery, chemotherapy, and radiation therapy have only marginally improved the prognosis for advanced GC, underscoring the urgent need for innovative therapeutic strategies. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a breakthrough in haematologic malignancies and is now being investigated as a potential treatment for solid tumours. The remarkable efficacy of CAR-T in GC has been demonstrated in both preclinical and clinical studies. Potential biomarkers for GC treatment include CLDN18.2, MSLN, CEA, EpCAM, MUC1, HER2, FOLR1, and NKG2DL. However, applying CAR-T cells directed against GC still faces considerable challenges. Novel CAR designs have the potential to enhance CAR-T cell therapy for GC by facilitating T cell infiltration, enhancing T cell persistence, reducing on-target off-tumour toxicity, improving tolerance to the immunosuppressive tumour microenvironment (TME), and bolstering interactions with heterogeneous antigens. This review summarises relevant preclinical studies and clinical progress in CAR-T cell therapy for GC, evaluates its therapeutic potential and safety, discusses current challenges, and outlines future directions for clinical translation.

论文信息

作者
Zhou J
单位
Innovation & Research Department, OriCell Therapeutics Co. Ltd, Shanghai, China. zhoujincai@oricell.com.China
文献类型
综述
期刊
British journal of cancer2025 Oct
原文标识
PubMed 40615715 · DOI 10.1038/s41416-025-03100-7