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靶向实体瘤CAR-T细胞设计: 安全性与通用性提升策略.

Chimeric antigen receptor gene-modified T (CAR-T) cell therapy represents an immunotherapeutic approach wherein autologous T cells are genetically engineered ex vivo to express specific chimeric antigen receptors (CARs), expanded, and reinfused into patients to specifically recognize and eliminate t...

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Publicado en:Chinese Journal of Cancer Biotherapy Vol. 32; no. 6; pp. 559 - 570
Autores principales: 邱毓灵, 廖天艺, 刘宝瑞, 李茹恬
Formato: review Journal Article
Publicado: Editorial Office of Chinese Journal of Cancer Biotherapy Jun2025
Acceso en línea:Ver este registro en EBSCOhost
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        1007385X
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      jtl: Chinese Journal of Cancer Biotherapy
      issn: 1007385X
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      dt: Jun2025
      vid: 32
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      pid: 39303
      pub: Editorial Office of Chinese Journal of Cancer Biotherapy
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        186905425
        186905425
        186905425
        10.3872/j.issn.1007-385x.2025.06.001
        186905425
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      formats:
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        atl: 靶向实体瘤CAR-T细胞设计: 安全性与通用性提升策略.
      aug:
        au:
          邱毓灵
          廖天艺
          刘宝瑞
          李茹恬
        affil: 南京大学医学院附属鼓楼医院 肿瘤中心, 江苏 南京 210008
      sug:
        subj:
          Neoplasms Therapy
          T Lymphocytes
          Cell Therapy
          Immunotherapy
          Genetic Engineering
          Patient Safety
          Immune System
          Cytokine Release Syndrome
          Antigens, Tumor
          Immune Checkpoint Inhibitors
          Immunologic Factors
      ab:
        Chimeric antigen receptor gene-modified T (CAR-T) cell therapy represents an immunotherapeutic approach wherein autologous T cells are genetically engineered ex vivo to express specific chimeric antigen receptors (CARs), expanded, and reinfused into patients to specifically recognize and eliminate tumor cells. Despite substantial efficacy in hematological malignancies, CAR-T cell therapy encounters significant barriers in solid tumors. Immune-related adverse events (irAEs), including cytokine release syndrome (CRS), compromise safety profiles, while tumor-associated antigen (TAA) heterogeneity restricts both single-target CAR-T cell applicability and universal CAR-T cell development. Consequently, breakthrough refinements remain essential for clinical translation in solid tumors. This review examines CAR-T cell therapy for solid tumors, critically evaluating safety and universality enhancement strategies through three core approaches: structural CAR design optimization, universal immune receptor retargeting, and antigen universality augmentation. Each approach undergoes systematic analysis of research pathways, advantages, and limitations, with future trajectories delineated. By synthesizing advances in safety and universal design paradigms, the review aims to establish innovative frameworks for CAR-T cell therapeutic development in solid tumor therapeutics.
        嵌合抗原受体基因修饰T 细胞（CAR-T 细胞）疗法是一种肿瘤免疫治疗方法: 来自人体的T 细胞在体外经遗传学修 饰、表达特异性嵌合抗原受体（CAR）, 然后将其回输入患者体内, 用于靶向识别和消除肿瘤细胞。尽管CAR-T细胞疗法在血液 系统肿瘤治疗中取得了较为显著的成功, 其在实体瘤治疗中仍面临障碍。细胞因子释放综合征（CRS）等免疫相关不良反应 （irAE）制约了CAR-T细胞的安全应用, 肿瘤相关抗原（TAA）的异质性限制了单一CAR-T细胞的广谱适用性, 也制约了其通用型 开发。鉴于此, 要使CAR-T 细胞疗法在实体瘤临床治疗中得到应用, 还需开展进一步的改良与提升研究。本文围绕实体瘤中 CAR-T细胞疗法, 从"CAR基因修饰策略"、"通用免疫受体的再靶向策略"及"抗原通用性'赋靶'策略"三个方面对CAR-T细胞领 域中为提高安全性和通用性所进行的探索进行述评, 系统剖析各策略的研究路径、优势及局限性, 并展望未来发展方向。通过综 述CAR-T细胞安全性和普适性设计策略的进展, 本文旨在为实体瘤的CAR-T细胞疗法研发提供创新思路.
      pubtype: Academic Journal
      doctype:
        review
        Journal Article
      ougenre: Article
    language: Chinese
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