TCR-T免疫治疗肿瘤:现状、挑战及展望

TCR-T immunotherapy for the treatment of solid tumor:current status,challenges and future prospects

T细胞受体工程T细胞(engineered T cell receptor-T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigens receptor-T cell,CAR-T)疗法是目前过继性T细胞治疗最有效的两种方式。由于CAR仅能识别肿瘤表面的抗原,在实体瘤治疗中至今未有令人满意的结果。TCR不仅能识别肿瘤表面抗原,同时能识别胞内抗原,因此,TCR-T疗法在治疗实体瘤方面显示出前所未有的前景,成为极具潜力的治疗方式。本综述探讨了TCR-T疗法与CAR-T疗法识别癌症抗原机制的差异及当前TCR-T疗法靶向的临床靶点和不同类型的肿瘤抗原,描述了TCR-T抗肿瘤治疗的临床开发现状,并讨论了临床前评估TCR效价的标准和目前TCR-T治疗的优势、存在的局限性及可能有效的应对措施。最后,我们回顾了TCR-T治疗的现状和当前仍存在的一些挑战,强调靶向肿瘤特异性抗原的重要性,概述了结合检查点阻断治疗和溶瘤病毒等的新抗原特异性TCR-T治疗策略,以期这种联合治疗能够显著改善癌症的免疫治疗效果,并对未来TCR-T治疗根除多发性癌症提供一些思路。

Engineered T cell receptor-T cell(TCR-T)therapy and chimeric antigen receptor-T cell(CAR-T)therapy are currently the two most effective ways of adoptive T cell therapy.Because CAR can only recognize antigens on the surface of tumors,CAR-T therapy has not yet had satisfactory results in the treatment of solid tumors.TCR can not only recognize tumor surface antigens,but also intracellular antigens.Thus TCR-T therapy has shown unprecedented promise in the treatment of solid tumors,and has become an extremely attractive treatment modality.This review described the differences between TCR-T therapy and CAR-T therapy in recognizing cancer antigens,the clinical targets and different types of tumor antigens targeted by current TCR-T therapy,the clinical development status of TCR-T antitumor therapy,and discussed the criteria for preclinical evaluation of TCR titer and the advantages,limitations and possible effective countermeasures of current TCR-T therapy.Finally,we reviewed the current status of TCR-T therapy and some of the challenges,emphasized the importance of targeting tumor-specific antigens,and outlined neoantigenspecific TCR-T treatment strategies combining checkpoint blockage therapy and oncolytic viruses,which we expect will significantly improve cancer immunotherapy and provide some clues for future TCR-T therapy to eradicate multiple types of cancer.