Potential Efficacy of Human IL-1RAP Specific CAR-T cell in Eliminating Leukemic Stem Cells of Chronic Myeloid Leukemia

Abstract

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.