人IL-1RAP特异性CAR-T细胞清除慢性粒细胞白血病白血病干细胞的潜在疗效

K. Zhao, Shushu Yuan, Lingling Yin, Jieyun Xia, K. Xu
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引用次数: 2

摘要

本报告的目的是评估IL1RAP特异性CAR-T细胞诱导IL1RAP阳性慢性髓性白血病细胞凋亡的作用。白血病干细胞(leukemia stem cells, LSCs)作为白血病复发的主要启动因子,目前仍不能彻底根除。尽管酪氨酸激酶抑制剂(TKI)彻底改变了慢性髓性白血病(CML)的治疗方法,但由于对静止LSCs没有反应,仅靠它并不能治愈这种疾病。Landberg N鉴定的人IL1RAP可作为CML中LSC的特异性表面标记物和肿瘤负荷指标。因此,IL1RAP嵌合抗体受体(CAR) T细胞特异性靶向LSCs可能是CML治疗的新策略。在这里,我们证明了IL1RAP CAR - T细胞对杀死IL1RAP阳性CML细胞系的细胞毒性比直接通过shRNA阻断IL1RAP表达的细胞毒性更强。此外,与shRAN组和空白载体处理组相比,IL1RAP CAR - T细胞共培养组白血病细胞的凋亡率更高,增殖率更低。总之,在本研究中,证明了一种潜在的创造性治疗靶点来消除LSCs和辅助治疗CML的策略。
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Potential Efficacy of Human IL-1RAP Specific CAR-T cell in Eliminating Leukemic Stem Cells of Chronic Myeloid Leukemia
The purpose of this report was to evaluate the effect of IL1RAP sepecifc CAR-T cell on inducing IL1RAP positive chronic myeloid leukemia cell apoptosis. Leukemic stem cells (LSCs) as the main initiating factor of leukemia relapse still cannot be eradicated thoroughly. Even though Tyrosine kinase inhibitors (TKI) revolutionized the therapy of chronic myeloid leukemia (CML), it alone does not cure this disease for the no response to quiescent LSCs. Human IL1RAP identified by Landberg N and we can be used as a specific surface marker and tumor burden indicator of LSC in CML. Therefore, IL1RAP chimeric antibody receptor (CAR) T cell specific targeting LSCs might be a novel strategy to CML therapy. Here, we demonstrated that IL1RAP CAR T cell showed more powerful cytotoxicity to kill IL1RAP positive CML cell lines than that to directly block IL1RAP expression by shRNA. Furthermore, compared with shRAN group and blank vector treated group, higher rate of apoptosis and lower proliferation of leukemia cells were showed in IL1RAP CAR T cell co-cultured group. In conclusion, in the present study a potential creative therapeutic target to eliminate LSCs and assistant strategy to cure CML was proved.
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