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The Effect of Regnase-1 Knockout on the Cytokine Secretion from Cord Blood Derived CAR-T Cells


( 1 School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; 2Department of Oncology, Western Theater General Hospital, Chengdu 610083, China; 3 Department of Obstetrics and Gynecology, Chengdu BOE Hosptial, Chengdu 610200, China; 4 Department of Hematology, Chengdu Fifth People’s Hospital, Chengdu 611130, China; 5 Basic Medical College of Chengdu Medical College, Chengdu 610500, China; 6 Medical College of Southwest Jiaotong University, Chengdu 610031, China)
Abstract:

As CAR-T (chimeric antigen receptor T) cells are continually modified to enhance their anti-tumor efficacy, attention must also be paid to the cytokine profiles secreted by activated CAR-T cells. These cytokines are important factors in causing the CRS (cytokine release syndrome), which is closely related to the clinical safety of CAR-T. Regnase-1 is a ribonuclease that negatively regulates the immune response. Using CRISPR/Cas9 gene editing technology, Regnase-1-deficient CAR-T cells derived from CB (cord blood) were successfully prepared. It was found that although the specific killing ability of Regnase-1CAR-T cells was significantly stronger than that of CAR-T cells, the secretion of pro-inflammatory cytokines by Regnase-1CAR-T cells was also significantly increased, indicating that Regnase-1CAR-T cells were potentially risky in terms of clinical safety


CSTR: 32200.14.cjcb.2024.02.0005