过继免疫细胞输注（adoptive cell transfer, ACT）属于肿瘤的被动免疫疗法。转移性黑素瘤患者在接受了ACT治疗后，部分患者肿瘤出现了持久的完全消退，显示了ACT在肿瘤治疗中的强大潜力。基因修饰淋巴细胞技术进一步为我们打开了肿瘤ACT治疗新领域的大门。肿瘤ACT治疗成功的关键在于如何鉴定出肿瘤细胞上合适的具有免疫原性的靶点，从而使得肿瘤浸润淋巴细胞（tumor infiltrating lymphocyte, TIL）或基因修饰淋巴细胞只攻击肿瘤细胞而不损伤正常组织。肿瘤组织过表达的分化抗原、共有非突变的肿瘤抗原以及肿瘤间质来源的抗原等大多在正常组织上有低水平表达，并非肿瘤ACT治疗的合适靶点。相反，共有突变的肿瘤特异性抗原、病毒癌基因编码的抗原以及个体肿瘤的独特驱动性突变产物有望成为肿瘤ACT治疗的理想靶点。越来越多的证据显示，未来肿瘤免疫治疗的进展很可能来自于免疫靶向个体肿瘤的独特的突变抗原，尤其是对肿瘤致癌性至关重要的基因的突变产物。

Adoptive cell transfer (ACT) is a passive immunotherapy of cancer. Recently, researchers have observed that durable complete cancer regressions can be achieved in patients with metastatic melanoma after ACT, encouragingly suggesting a great potential for ACT in the treatment of cancer in clinical settings. This potential can be further enhanced when genetic modification of lymphocytes is performed. The key to the success of adoptive cell therapy is the identification of suitable immunologic targets on cancer cells that can be attacked by tumor infiltrating lymphocytes (TIL) or genetically modified lymphocytes without damaging normal tissues. Differentiation antigens overexpressed on cancers, shared non-mutated antigens of cancers, and antigens from tumor stroma are not suitable targets of ACT due to their low level expression in normal tissues. On the contrary, antigens encoded by shared mutations, viral oncogenes, or unique driver mutations may serve as ideal targets of ACT. Further development of ACT will result from new adoptive cell immunotherapy strategies with lymphocytes that recognize mutated antigens, in particular those derived from gene products that are involved in carcinogenesis.

国家科技支撑计划资助项目（No.2015BAI12B12);天津市应用基础与前沿技术研究计划资助项目（No.13JCYBJC41400, No.14JCTPJC00476)。