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结直肠癌的过继性免疫细胞治疗

英文原题:Adoptive immune cell therapy for colorectal cancer.

PubMed 2025/04/01(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

结直肠癌(CRC)是全球癌症相关发病和死亡的主要原因,晚期患者的治疗选择有限。

中文摘要

结直肠癌(CRC)是全球癌症相关发病和死亡的重要原因,晚期患者的治疗选择有限。免疫疗法,特别是基于免疫细胞的疗法,作为靶向CRC的创新策略受到广泛关注。本综述总结多种免疫细胞疗法的进展,包括树突状细胞疫苗、CAR/TCR-T细胞、CAR-NK细胞等;这些细胞经工程化后能够识别并攻击表达特定抗原的癌细胞。CAR-T疗法已成功用于血液系统恶性肿瘤,但在CRC中受实体瘤微环境限制,细胞浸润和持续存在不足。CAR-NK、CAR-M和CAR-γδT细胞则因具有无需预先致敏即可靶向肿瘤细胞、诱发严重细胞因子释放综合征风险较低等独特特点,提供了替代策略。近期慢病毒转导技术进步已可在NK和T细胞上有效表达CAR,并在CRC模型中取得有希望的临床前结果。本综述探讨这些疗法的机制、肿瘤靶点、临床前研究和早期临床试验,并讨论提高肿瘤抗原特异性、克服免疫抑制性肿瘤微环境等关键挑战。文中还讨论免疫检查点抑制剂和细胞因子疗法等联合治疗改善免疫细胞疗法疗效的潜力。仍需持续研究,以推动这些有前景的方法转化至临床,为CRC患者带来新的希望。

展开英文摘要原文

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, with limited options for patients at advanced stages. Immunotherapy, particularly immune cell-based therapies, has gained significant attention as an innovative approach for targeting CRC. This review summarizes the progress in various immune cell therapies, including DC vaccine, CAR/TCR-T cells, CAR-NK cells et al, each engineered to recognize and attack cancer cells expressing specific antigens. CAR-T cell therapy, which has been successful in hematologic cancers, faces challenges in CRC due to the solid tumor microenvironment, which limits cell infiltration and persistence. CAR-NK cells, CAR-M and CAR- T cells, however, offer alternative strategies due to their unique properties, such as the ability to target tumor cells without prior sensitization and a lower risk of inducing severe cytokine release syndrome. Recent advances in lentiviral transduction have enabled effective expression of CARs on NK and T cells, providing promising preclinical results in CRC models. This review explores the mechanisms, tumor targets, preclinical studies, and early-phase clinical trials of these therapies, addressing key challenges such as enhancing specificity to tumor antigens and overcoming the immunosuppressive tumor microenvironment. The potential of combination therapies, including immune checkpoint inhibitors and cytokine therapy, is also discussed some as a means to improve the effectiveness of immune cell-based treatments for CRC. Continued research is essential to translate these promising approaches into clinical settings, offering new hope for CRC patients.

论文信息

作者
Liu C、Liu N、Zhang T、Tu Y
第一作者单位
Guangdong Province Science and Technology Expert Workstation, Huizhou Central People's Hospital, Huizhou, Guangdong, China.China
通讯作者单位
Science Research Center, Huizhou Central People's Hospital, Huizhou, Guangdong, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 40236691 · DOI 10.3389/fimmu.2025.1557906