TCR在识别肿瘤细胞，启动CTLs应答中发挥关键作用。慢性粒细胞白血病（CML）患者，白血病特异TCR亚型缺乏，不能触发足够的CTLs应答。基于改进TCR对肿瘤细胞识别力的TCR-T疗法有望提高CML特异CTLs应答。BCR-ABL是CML特异的胞浆抗原，非常适合作为抗原靶点开发TCR-T疗法。我们前期用负载BCR-ABL的树突状细胞激活CD8+T细胞，诱导了BCR-ABL特异CTLs应答。本项目拟从含有CTLs的T细胞群中分离BCR-ABL特异CTLs克隆，采用RACE PCR结合DNA测序鉴定BCR-ABL特异TCR亚型，融合iCasp9安全开关和CD8协同受体，克隆入慢病毒载体，制备高效、安全的新型TCR-T细胞，并探讨其在活体内、外对CML细胞的CTLs效应。项目研究结果有助于阐明BCR-ABL特异CTLs应答的TCR识别机制，为CML提供一种高效、安全的新型TCR-T疗法。

T cell receptors (TCR) are crucial in recognizing tumor cells and eliciting cytotoxic lymphocytes (CTLs) response. Deficiency of leukemic TCR subtype contributes to weak CTLs response in patients with CML. TCR-T therapy with improved recognition of tumor cells is expected to enhance CML specific CTLs response. BCR-ABL is a specific cytoplasmic antigen, which is very suitable to serve as an antigen target to develop TCR-T therapy. In our precious studies, CD8+ T cells were impulsed with dendritic cells loaded with BCR-ABL, which induced BCR-ABL specific CTLs response. In this study, we plan to isolate BCR-ABL specific CTLs clone, and identify BCR-ABL specific TCR subtype by RACE PCR and DNA sequencing. BCR-ABL specific TCR fused with iCasp9 safety switch and CD8 coreceptor is cloned into a lentivirus vector, and trancduces T cells to establish a novel kind of TCR-T cells with high efficiency and safety. In this project, the CML specific CTLs response would be investigated in vitro and in vivo. The research results are expected to elucidate the exact TCR subtype that elicits BCR-ABL specific CTLs response and provide a novel TCR-T therapy with high efficiency and safety for CML patients.