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CAR 为基础的细胞治疗在胃肠道恶性肿瘤中的临床试验概况

英文原题:Clinical trial landscape of CAR-based cell therapy for gastrointestinal malignancies.

PubMed 2026/03/10(内容时间) J Immunother Cancer Q1 · IF 11.7(JCR 2025)

研究概要

胃肠道恶性肿瘤(GIM)给全球健康带来了沉重负担,约占全球癌症相关死亡率的33%。

中文摘要

胃肠道恶性肿瘤(GIM)构成了重大的全球健康负担,约占全球癌症相关死亡率的33%。尽管基于嵌合抗原受体(CAR)的细胞疗法在血液系统恶性肿瘤中取得了显著成功,但其在实体瘤尤其是GIM中的应用仍处于起步阶段。本综合性全景分析通过从Trialtrove数据库检索截至2025年10月的179项符合条件的临床试验,系统考察了CAR细胞疗法治疗GIM的临床试验生态系统(肝胆和胰腺恶性肿瘤被排除在外)。分析揭示了一个以早期阶段为主的格局,其中I期研究占所有试验的70.39%。在地理分布上,中国(70.77%)和美国(16.41%)主导了试验的发起,而学术机构赞助了54.92%的研究。Claudin 18.2、NKG2D(L)、间皮素和CEA是最常被靶向的抗原。经外周静脉输注的自体疗法是主要的治疗模式。联合化疗和免疫治疗的策略展现出有前景的协同潜力,提示多模式方法可能增强治疗效果,同时可能减轻耐药机制。创新性临床前进展与日益支持的监管框架的汇聚预示着该领域的变革性进展,将CAR细胞疗法定位为抗GIM治疗武器库中新兴的基石模式。

展开英文摘要原文

Gastrointestinal malignancies (GIM) impose a substantial global health burden, accounting for approximately 33% of cancer-related mortality worldwide. Although chimeric antigen receptor (CAR)-based cell therapy has achieved remarkable success in hematological malignancies, its application in solid tumors, particularly GIM, remains in its nascent stages. This comprehensive landscape analysis systematically examined the clinical trial ecosystem of CAR-based cell therapy for GIM by retrieving 179 eligible trials from the Trialtrove database as of October 2025 (hepatobiliary and pancreatic malignancies were excluded). The analysis revealed a predominantly early-phase landscape, with Phase I studies constituting 70.39% of all trials. Geographically, China (70.77%) and the USA (16.41%) dominated trial initiation, while academic institutions sponsored 54.92% of investigations. Claudin 18.2, NKG2D(L), mesothelin, and CEA emerged as the most frequently targeted antigens. Autologous therapy administered via peripheral intravenous infusion represented the predominant therapeutic modality. Combination strategies incorporating chemotherapy and immunotherapy demonstrated promising synergistic potential, suggesting that multimodal approaches may enhance therapeutic efficacy while potentially mitigating resistance mechanisms. The convergence of innovative preclinical developments with increasingly supportive regulatory frameworks portends transformative advances in the field, positioning CAR-based cell therapy as an emerging cornerstone modality in the therapeutic armamentarium against GIM.

论文信息

作者
Li W、Yang J、Kong Q、Chen Z
第一作者单位
Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.China
通讯作者单位
Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China chenzheyu@scu.edu.cn.China
文献类型
综述
期刊
Journal for immunotherapy of cancer2026 Mar 10
原文标识
PubMed 41807034 · DOI 10.1136/jitc-2025-014286