The Effect of Regnase-1 Knockout on the Function of Cord Blood-Derived CAR-T Cells

LIU Jiahui^1,2, RAN Fengping³, MENG Lu⁴, ZHAO Ri⁵, LI Hua²*

(¹School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; ²Department of Oncology, Western Theater General Hospital, Chengdu 610083, China; ³Department of Gynaecology and Obstetrics, Chengdu BOE hosptial, Chengdu 610200, China; ⁴Scientific Research and Experimental Center,Chengdu Medical College, Chengdu 610500, China; ⁵Medical College of Southwest Jiaotong University, Chengdu 610031, China)

Abstract:

Although CAR-T (chimeric antigen receptor-T) cell therapy is effective in the treatment of hematologic tumors, it still faces the problem of short persistence of CAR-T cells in vivo, which is closely related to the clinical efficacy. Regnase-1 has a ribonuclease effect and negatively regulates the immune response. In this study, regnase1-deficient CAR-T cells delivered from cord blood T cells were prepared. The Regnase-1 deletion did not affect either the expression of CAR molecules of cord blood T cells or the proliferation or the differentiation of CAR-T cells in vitro. CD39, an exhausted T cell marker, could be significantly inhibited at the early stage of CAR-T growth in vitro. Regnase-1 kncokout enhanced the specific killing ability and increased amplication of CAR-T, which helps to improve cord blood-derived CAR-T cell persistence and lays a foundation for the optimization of CAR-T cell drugs.

CSTR: 32200.14.cjcb.2023.10.0005