Ouladan Shaida, Orouji Elias
Department of Pathology, McGill University, Montreal, QC, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
J Clin Oncol. 2025 Mar 10;43(8):994-1005. doi: 10.1200/JCO-24-02081. Epub 2025 Jan 13.
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.
结直肠癌(CRC)仍然是一项重大的全球健康负担,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,但转移性CRC患者往往面临选择有限和预后不佳的情况。嵌合抗原受体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一条有前景的途径。本综述通过分析临床试验并突出显著的CRC特异性靶点,探讨了CAR-T细胞疗法在CRC中的潜力。我们讨论了诸如免疫抑制微环境、肿瘤异质性和限制CAR-T疗效的物理屏障等挑战。新兴策略,如逻辑门控和双靶向CAR-T细胞,提供了克服这些障碍的实际解决方案。此外,我们探索了CAR-T细胞疗法与免疫检查点抑制剂的联合使用,以增强T细胞的持久性和肿瘤浸润。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。