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结直肠癌中的 CAR-T 细胞:开创实体瘤免疫治疗新途径

英文原题:Chimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy.

PubMed 2025/01/13(内容时间) J Clin Oncol Q1 · IF 44.7(JCR 2025)

研究概要

结直肠癌(CRC)仍是全球主要的健康负担,是最常见的癌症之一,死亡率高。

中文摘要

结直肠癌(CRC)仍是全球主要的健康负担,是最常见且死亡率高的癌症之一。尽管传统治疗方式取得了进展,转移性CRC患者仍常面临治疗选择有限和预后不佳的困境。CAR-T(CAR-T)细胞疗法最初在血液系统恶性肿瘤中取得成功,为治疗包括CRC在内的实体瘤提供了有前景的途径。本综述通过分析临床试验并重点介绍突出的CRC特异性靶点,探讨了CAR-T细胞疗法在CRC中的潜力。我们讨论了限制CAR-T疗效的挑战,如免疫抑制性微环境、肿瘤异质性和物理屏障。新兴策略,如逻辑门控和双靶向CAR-T细胞,为克服这些障碍提供了切实可行的解决方案。此外,我们探讨了CAR-T细胞疗法与免疫检查点抑制剂的联合应用,以增强T细胞持久性和肿瘤浸润。随着该领域的不断发展,CAR-T细胞疗法在彻底改变CRC治疗格局方面具有巨大潜力。

展开英文摘要原文

Colorectal cancer (CRC) remains a major global health burden, being one of the most prevalent cancers with high mortality rates. Despite advances in conventional treatment modalities, patients with metastatic CRC often face limited options and poor outcomes. Chimeric antigen receptor-T (CAR-T) cell therapy, initially successful in hematologic malignancies, presents a promising avenue for treating solid tumors, including CRC. This review explores the potential of CAR-T cell therapy in CRC by analyzing clinical trials and highlighting prominent CRC-specific targets. We discuss the challenges such as immunosuppressive microenvironment, tumor heterogeneity, and physical barriers that limit CAR-T efficacy. Emerging strategies, such as logic-gated and dual-targeting CAR-T cells, offer practical solutions to overcome these hurdles. Furthermore, we explore the combination of CAR-T cell therapy with immune checkpoint inhibitors to enhance T-cell persistence and tumor infiltration. As the field continues to evolve, CAR-T cell therapies hold significant potential for revolutionizing the treatment landscape of CRC.

论文信息

作者
Ouladan S、Orouji E
第一作者单位
Department of Pathology, McGill University, Montreal, QC, Canada.Canada
通讯作者单位
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.Canada
文献类型
综述 · 非美国政府资助研究
期刊
Journal of clinical oncology : official journal of the American Society of Clinical Oncology2025 Mar 10
原文标识
PubMed 39805063 · DOI 10.1200/JCO-24-02081