Construction of the Fourth-Generation CAR-T Cells Targeting CD138 and Functional Research
LIU Yu, ZHENG Ru, XIE Jinhai, GAO Jimin*
This study constructed a fourth-generation CAR-T cell targeting CD138 (secreting IL-7 and CCL19), and compared the biological function with the second-generation CAR-T cell targeting CD138 to explore the advantages of the fourth-generation CAR-T cell in clinical application. The second and fourth generation CART cells targeting CD138 were prepared by transfecting T cells of healthy human peripheral blood with lentivirus. Then, the CFSE proliferation experiment, chemotaxis chamber, ELISA method and flow cytometry were performed to detect the cell proliferation ability, chemotaxis ability, cytokine secretion, CAR expression rate and subtype. The killing function of CAR-T cells on multiple myeloma cell lines in vitro was detected by luciferase bioluminescence method; an NCG mouse model of human multiple myeloma was constructed, and the tumor regression after CART cells infusion was monitored by a bioluminescence imaging system. The results showed that the fourth-generation CAR-T cell targeting CD138 (CD138-BBZ-7×19) had better biological functions than the second-generation CART cell (CD138-BBZ) in vitro, and it had obvious antitumor effect in animal models of human multiple myeloma.
CN
EN