Functional validation and improvement of chimeric antigen receptor T cells targeting CD7
10.3760/cma.j.cn112309-20230803-00025
- VernacularTitle:靶向CD7嵌合抗原受体T细胞的功能验证及改进的初步探索
- Author:
Yi ZHANG
1
;
Jiaxi WANG
;
Rui ZHANG
;
Mingfeng ZHAO
Author Information
1. 天津医科大学一中心临床医学院血液科，天津 300380
- Keywords:
Chimeric antigen receptor T cells;
CD7;
Dasatinib;
Functional verification
- From:
Chinese Journal of Microbiology and Immunology
2024;44(11):926-934
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To validate the efficacy of chimeric antigen receptor T cells targeting CD7 (CD7 CAR-T cells) modified with protein blocking technology and analyze whether pretreatment with dasatinib can enhance CD7 CAR-T killing ability or reverse the depletion phenotype.Methods:Green fluorescent protein (GFP)-labeled tumor cells were co-incubated with CD7 CAR-T cells or T cells at different potency-to-target ratios, but the culture volume and the numbers of CAR-T/T cells were same. The number of tumor cells was detected using flow cytometry. The killing effect of CAR-T cells on tumor cells was evaluated. A mouse model of acute T-lymphoblastic leukemia (T-ALL) was constructed by injecting 1×10 6 luciferase-expressing CCRF-CEM cells into the mouse tail vein to evaluate the therapeutic effect of CD7 CAR-T cells. Results:CD7 CAR-T cells had a significant killing effect on CCRF-CEM and Jurkat cells, but not on CD7-negative NALM6 cells. The mice in the group receiving CD7 CAR-T cells had a significantly reduced in vivo tumor load and a significantly prolonged survival time as compared with the mice in the group receiving untransduced T cells ( P<0.05). Dasatinib pretreatment significantly reversed the depletion phenotype of CD7 CAR-T cells ( P<0.05) and had no adverse effects on the killing effect and the proliferation of the cells. Conclusions:Protein-blocking technology-modified CD7 CAR-T cells are protected from killing each other, and pretreatment with dasatinib is expected to improve the efficacy and durability of CD7 CAR-T cells.
