T-ALL Cells as Tool Cells for CAR T Therapy.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T cell malignancies, especially in T-ALL. The main reason for CAR T therapy limitations is that T-ALL cells and normal T cells share antigens, which improves the difficulty of sorting pure T cells, resulting in product contamination, and would lead to CAR T cell fratricide. Thus, we considered creating a CAR on T-ALL tumor cells (CAR T-ALL) to prevent fratricide and eliminate tumor cells. We found that T-ALL cells transduced with CAR would actually commit fratricide. However, CAR T-ALL could kill only tumor cells on T-ALL cell lines, and other types of tumor cells had no killing function after being transferred with CAR. Furthermore, we created CD99 CAR with expression controlled by the Tet-On system on Jurkat cells, which could avoid the fratricide of CAR T-ALL during proliferation, ensuring the controllability of the killing time and effect. Jurkat transduced with a CAR-targeting antigen, which was expressed on other cancer cells, could kill other cancer cell lines, demonstrating that T-ALL cells could be used as tool cells for cancer therapy. Our study supplied a new feasible treatment regimen for cancer treatment in the clinic.