IL1RAP 嵌合受体T 细胞疫苗抗慢性髓系白血病干细胞的研究

项目名称： IL1RAP 嵌合受体T 细胞疫苗抗慢性髓系白血病干细胞的研究

项目编号： No.81200376

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 赵恺

作者单位： 徐州医学院

项目金额： 23万元

中文摘要： 慢性髓系白血病（CML）是一种严重威胁人类健康和生命的疾病，目前临床中各种治疗方法均存在缺陷，不能有效清除白血病干细胞（LSC）是导致疾病复发的根源之一。特异性杀伤LSC是CML治疗的关键。最新研究表明，IL1RAP是区分CML中LSC和正常造血干细胞（HSC）最特异的表面标志。研究证实虽然IL1RAP抗体能杀灭白血病细胞系及CML患者体内的LSC，但IL1RAP抗体可被血浆中可溶性IL1RAP中和而失效，需持续应用且不能对新发LSC起免疫监视作用。本课题拟构建通过非MHC限制性途径识别LSC的IL1RAP嵌合受体(CAR) T细胞疫苗，经体外及体内实验，证实CAR-T细胞疫苗杀伤CML细胞系效果及在体内对LSC生物学行为影响，阐明疫苗自身的功能特征及杀伤机制。如期完成，可通过使用本疫苗有效清除CML中LSC，为CML的临床治疗提供新途径。

中文关键词： 慢性髓系白血病；白细胞介素1受体辅助蛋白；嵌合T细胞；疫苗；白血病干细胞

英文摘要： Chronic myeloid leukemia (CML) is a great threat to people's health and life.All of the therapies against CML still have shortcomings, which can not eliminate leukemic stem cell (LSC) leading to the relapse of CML. The key step of therapy for CML is specific cleaning of LSC. Recently it is reported that the specific surface marker to distinct LSC and normal haemopoietic stem cell (HSC) is IL1RAP. Furthermore, the antibody of IL1RAP can effectively lysis leukemic cell lines and LSCs in CML patients. However, there are many limitations in utilization of IL1RAP antibody, including neutralization by soluble IL1RAP in plasma, necessity of persistent injection and lack of immunologic surveillance to neo-tumor cells. In this project, we will design an IL1RAP chimeric antibody receptor(CAR) T cell vaccine which can recognize LSC in a specific and non-MHC restricted pattern. Meanwhile, we will illuminate the influence produced by IL1RAP-CAR T cell vaccine to LSC, as well as the function properties of T cell vaccine. As scheduled, it will verify the novel target to eliminate LSC and will provide precious information to cure CML.

英文关键词： CML；IL1RAP；CAR-T cell；vaccine；LSC