Potential Efficacy of Human IL-1RAP Specific CAR-T cell in Eliminating Leukemic Stem Cells of Chronic Myeloid Leukemia
Potential Efficacy of Human IL-1RAP Specific CAR-T cell in Eliminating Leukemic Stem Cells of Chronic Myeloid Leukemia
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人IL-1RAP特异性CAR-T细胞消除慢性粒细胞白血病干细胞的潜在功效
DOI：
10.4172/2329-6917.1000232
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Kailin Xu
中科院分区：
文献类型：
--
作者：
Kai Zhao;Shushu Yuan;Lingling Yin;Jieyun Xia;Kailin Xu
本研究旨在探讨IL 1 RAP特异性CAR-T细胞诱导IL 1 RAP阳性慢性髓系白血病细胞凋亡的作用。白血病干细胞作为白血病复发的主要始动因素，至今仍无法彻底根除。尽管酪氨酸激酶抑制剂（TKI）彻底改变了慢性粒细胞白血病（CML）的治疗，但它本身并不能治愈这种对静止LSC无反应的疾病。人IL 1 RAP由Landberg N鉴定，我们可以将其用作CML中LSC的特异性表面标志物和肿瘤负荷指标。因此，IL 1 RAP嵌合抗体受体（CAR）T细胞特异性靶向LSC可能是CML治疗的新策略。在这里，我们证明了IL 1 RAP CAR T细胞对IL 1 RAP阳性CML细胞系的杀伤作用比通过shRNA直接阻断IL 1 RAP表达更强。与shRAN组和空白载体组相比，IL 1 RAP CAR T细胞共培养组白血病细胞的凋亡率更高，增殖率更低。结论：本研究为消除LSC提供了一个潜在的治疗靶点，为CML的治疗提供了一个新的辅助策略。
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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DOI：
10.1073/pnas.1004408107
发表时间：
2010-09-14
影响因子：
11.1
作者：
Jaras, Marcus;Johnels, Petra;Fioretos, Thoas
通讯作者：
Fioretos, Thoas
带有嵌合抗原受体的T细胞具有有效的抗肿瘤作用，可以在晚期白血病患者中建立记忆。
影响因子：
17.1
作者：
Kalos M;Levine BL;Porter DL;Katz S;Grupp SA;Bagg A;June CH
通讯作者：
June CH
影响因子：
10.1
作者：
A. Carella;J. Goldman;G. Martinelli;J. Melo;D. Perrotti
通讯作者：
A. Carella;J. Goldman;G. Martinelli;J. Melo;D. Perrotti
影响因子：
3.3
作者：
Jabbour EJ;Cortes JE;Kantarjian HM
通讯作者：
Kantarjian HM
DOI：
10.1056/nejmoa1103849
发表时间：
2011-08-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Porter DL;Levine BL;Kalos M;Bagg A;June CH
通讯作者：
June CH