肿瘤细胞治疗研究
英文原题：Advances in CAR-T cell therapy for malignant solid tumors.
经嵌合抗原受体（CAR）修饰的T细胞具有不依赖主要组织相容性复合体识别肿瘤相关抗原的优势，因此能够实现对肿瘤靶点的高效应答。
经嵌合抗原受体（CAR）修饰的T细胞具有不依赖主要组织相容性复合体识别肿瘤相关抗原的优势，因此可实现对肿瘤靶点的高效应答。嵌合抗原受体（CAR）T细胞疗法在血液系统恶性肿瘤中已显示出良好的治疗效果；然而，其对实体瘤的疗效普遍不令人满意。原因包括实体瘤缺乏肿瘤特异性抗原靶点、工程化T细胞归巢能力的不确定性以及肿瘤的抑制性免疫微环境。在临床试验中，CAR-T细胞治疗实体瘤的靶点主要为双唾液酸神经节苷脂（GD2）、紧密连接蛋白18亚型2（CLDN18.2）、间皮素、B7同源物3（B7H3）、磷脂酰肌醇蛋白聚糖（GPC）3和表皮生长因子受体变异体（EGFRv）。CAR-T细胞与溶瘤病毒、酪氨酸激酶抑制剂和程序性死亡配体-1单克隆抗体联合使用可能提高其疗效。实体瘤的CAR-T细胞疗法可通过基因编辑进行优化，以增强CAR-T细胞的活性，添加相应的调控组件使CAR-T细胞的激活更安全、更可控，并增强CAR-T细胞的持久性。本文综述了CAR-T细胞疗法在实体瘤中的最新进展，为临床应用提供新的见解。经嵌合抗原受体（CAR）修饰的T细胞具有不依赖主要组织相容性复合体识别肿瘤相关抗原的优势，因此可实现对肿瘤靶点的高效应答。嵌合抗原受体（CAR）T细胞疗法在血液系统恶性肿瘤中已显示出良好的治疗效果；然而，其对实体瘤的疗效普遍不令人满意。原因包括实体瘤缺乏肿瘤特异性抗原靶点、工程化T细胞的归巢能力不确定以及肿瘤的抑制性免疫微环境。在临床试验中，CAR-T细胞治疗实体瘤的靶点主要包括双唾液酸神经节苷脂（GD2）、claudin-18异构体2（CLDN18.2）、间皮素、B7同源物3（B7H3）、磷脂酰肌醇蛋白聚糖（GPC）3和表皮生长因子受体变体（EGFRv）。CAR-T细胞与溶瘤病毒、酪氨酸激酶抑制剂和程序性死亡配体-1单克隆抗体联合使用可能提高其疗效。实体瘤的CAR-T细胞治疗可以通过基因编辑来优化，以增强CAR-T细胞的活性，添加相应的调控组件使CAR-T细胞的激活更安全、更可控，并增强CAR-T细胞的持久性。本文综述了CAR-T细胞治疗实体瘤的最新进展，为临床应用提供新的见解。
T cells modified by chimeric antigen receptor (CAR) have the advantage of major histocompatibility complex-independent recognition of tumor-associated antigens, so can achieve efficient response to tumor targets. Chimeric antigen receptor (CAR) T cell therapy has shown a good therapeutic effect in hematological malignancies; however, its efficacy is generally not satisfactory for solid tumors. The reasons include the lack of tumor specific antigen target on solid tumors, the uncertainty of homing ability of engineered T cells and the inhibitory immune microenvironment of tumors. In clinical trials, the targets of CAR-T cell therapy for solid tumors are mainly disialoganglioside (GD2), claudin-18 isoform 2 (CLDN18.2), mesenchymal, B7 homolog 3 (B7H3), glypican (GPC) 3 and epidermal growth factor receptor variant (EGFRv ) . Combination of CAR-T cells with oncolytic viruses, tyrosine kinase inhibitors, and programmed death ligand-1 monoclonal antibodies may increase its efficacy. The CAR-T cell therapy for solid tumors can be optimized through gene editing to enhance the activity of CAR-T cells, adding corresponding regulatory components to make the activation of CAR-T cells safer and more controllable, and enhancing the persistence of CAR-T cells. In this article, we review the latest advances of CAR-T cell therapy in solid tumors to provide new insights for clinical application. T cells modified by chimeric antigen receptor (CAR) have the advantage of major histocompatibility complex-independent recognition of tumor-associated antigens, so can achieve efficient response to tumor targets. Chimeric antigen receptor (CAR) T cell therapy has shown a good therapeutic effect in hematological malignancies; however, its efficacy is generally not satisfactory for solid tumors. The reasons include the lack of tumor specific antigen target on solid tumors, the uncertainty of homing ability of engineered T cells and the inhibitory immune microenvironment of tumors. In clinical trials, the targets of CAR-T cell therapy for solid tumors are mainly disialoganglioside (GD2), claudin-18 isoform 2 (CLDN18.2), mesenchymal, B7 homolog 3 (B7H3), glypican (GPC) 3 and epidermal growth factor receptor variant (EGFRv ) . Combination of CAR-T cells with oncolytic viruses, tyrosine kinase inhibitors, and programmed death ligand-1 monoclonal antibodies may increase its efficacy. The CAR-T cell therapy for solid tumors can be optimized through gene editing to enhance the activity of CAR-T cells, adding corresponding regulatory components to make the activation of CAR-T cells safer and more controllable, and enhancing the persistence of CAR-T cells. In this article, we review the latest advances of CAR-T cell therapy in solid tumors to provide new insights for clinical application.
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