T细胞受体基因工程T细胞治疗的现状与未来

免疫治疗为肿瘤的治疗带来了新的契机和希望，其中免疫检查点抑制剂、治疗性抗体、肿瘤疫苗、免疫调节剂、过继细胞治疗等显著改善了肿瘤患者的预后，部分晚期肿瘤患者获得了长期生存。T细胞受体基因工程T细胞（T cell receptor-engineered T cell，TCR-T）治疗是将识别肿瘤抗原的T细胞受体（T cell receptor，TCR）导入到患者的外周T细胞中，制备能够特异性识别肿瘤抗原的T细胞，然后将这些基因工程T细胞回输患者的治疗方法。该疗法采用天然的TCR信号，具有更高的治疗潜力和更低的毒性或副作用，并且TCR能够识别更多的肿瘤抗原，因此具有广泛的应用前景。目前，多项TCR-T治疗的临床研究正在开展，现有结果表明TCR-T具有较好的治疗效果，但也存在副作用等问题亟需解决。综述TCR-T治疗的临床研究进展、目前面临的挑战以及未来发展的方向。

Current and Future Development of T Cell Receptor-Engineered T Cell Therapy

Immunotherapy has brought us new opportunities and hopes in cancer treatment, including immune checkpoint inhibitors, therapeutic antibodies, cancer vaccines, immune modulators and adoptive cell therapies, which have significantly improved prognosis of tumor patients and long-term survival of some advanced malignant tumor patients. T cell receptor-engineered T cell(TCR-T) therapy is a type of therapy that transforms T cell receptor(TCR)-recognizing tumor antigens into the patient,s peripheral T cells to produce T cells which can specifically recognize tumor antigens, with such genetically engineered T cells being then injected back into the patient. Due to the natural TCR signaling, better therapeutic efficacy, lower toxic or side effects and more options of targeting antigens, TCR-T therapy is believed to have a wide range of application. At present, a number of clinical studies on TCR-T therapy are underway, and the existing results show that TCR-T has a good therapeutic effect, though some problems such as side effects still remain to be addressed. This review focuses on the clinical research progress, current challenges and future development of TCR-T therapy.