基因修饰T细胞疗法在肿瘤治疗领域取得突破性进展，主要包括嵌合抗原受体基因修饰T（chimeric antigen receptor engineered T，CAR-T）细胞和T细胞受体基因修饰T（T-cell receptor modified T，TCR-T）细胞。虽然CAR-T细胞疗法在血液系统 肿瘤治疗领域呈现良好的临床治疗效果，但CAR-T细胞仅能识别肿瘤细胞膜抗原（占细胞全部抗原的比例约10%），而TCR-T细 胞可以识别人白细胞抗原（human leukocyte antigen，HLA）提呈的细胞内抗原，因此TCR-T细胞可以识别更多种类的肿瘤抗原，进 而实现对CAR-T细胞的合理补充。由于TCR-T细胞需要同时识别细胞内抗原和对应的HLA，而不同患者的HLA分型和表达的 肿瘤抗原都可能存在巨大差异，因此有必要为每个/每类肿瘤患者定制个体化的TCR-T细胞，其中的关键为筛选特异识别肿瘤抗 原的TCR。当前主要有筛选靶向“已知”肿瘤抗原TCR和筛选靶向“未知”肿瘤抗原TCR的两种策略，但其各有适用性，应针对每 个患者制定适合的筛选方法，以制备多种肿瘤特异性TCR-T细胞，从而实现个体化TCR-T细胞的肿瘤治疗。

Genetically engineered T cell immunotherapy has made breakthroughs in the field of tumor therapy, including chimeric antigen receptor engineered-T (CAR-T) cells and T cell receptor modified-T (TCR-T) cells. Although CAR-T cell therapy presents an attractive clinical efficacy on treatment of hematological tumors, CAR-T cells can only recognize tumor cell membrane antigens (accounting for approximately 10% of all cellular antigens); However, TCR-T cells can recognize intracellular antigens presented by human leukocyte antigens (HLAs), so TCR-T cells can recognize more types of tumor antigens, and then realize a reasonable supplement to CAR-T cells. TCR-T cells needs to recognize both intracellular antigens and corresponding HLAs, while the HLA types and tumor antigens in different patients may present huge difference, therefore, it is necessary to customize individualized TCR-T cells for each/each type of cancer patient, in which screening the TCR that specifically recognizes tumor antigens is the key point. Currently, there are two main strategies for screening TCR, targeting "known" tumor antigens and targeting "unknown" tumor antigens, and each has its own applicability. A suitable screening method should be developed for each patient to prepare a variety of tumor-specific TCR-T cells, so as to achieve individualized TCR-T cell therapy for tumor treatment.

国家自然科学基金资助项目（No. 81972880, No. 82003246）