In Vitro Construction and Preliminary Functional Identification of Universal CD19 CAR-T
MENG Lu1,2, ZHAO Ri3,4, ZHOU Dan1,2, LIU Jiahui4,5, ZHANG Yao3,4, ZHANG Yueqin2,6, LIU Qin2,6, LIU Yang2,6, ZHANG Yue4,7, HU Shubo1,2, ZHANG Shiqin1,2, LI Hua4, ZOU Qiang1,2*
CAR-T immune cell therapy has made breakthrough progress in the field of hematological tumors. However, the CAR-T cells currently on the market and in domestic clinical trials are all derived from tumor patients themselves, that is, autologous CAR-T. Restricted by the quality and quantity of patient T cells, long preparation cycle and high price, it is difficult to apply them in large-scale clinical applications. In this study, CRISPR/Cas9 gene editing technology was used to knock out TCR molecules and HLA-I molecules in T cells derived from healthy human umbilical cord blood to avoid immune rejection caused by allogeneic cell therapy. CAR gene was transduced by lentiviral vector to prepare universal CD19 CAR-T cell drugs. It is proved that it can reduce immune rejection in vitro and has a strong killing effect on target cells in vitro. This method provides a way to produce universal CAR-T cells. Firstly, it is expected to make more patients to receive timely treatment and makes it possible to repeat treatment. Secondly, it reduces the manufacturing cost of CAR-T therapy, thereby reducing the burden of patients. Finally, it provides experimental basis for clinical treatment.
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