Discovery of a novel envelope protein derived from simian retrovirus 2 for pseudotyping retroviral vectors used for production of CAR immune cells

Abstract

Abstract In this study, we develop a simian retrovirus 2 pseudotyped retrovirus (SRV2 RV) for the generation of CAR-based immune cells. The SRV2 RV exhibits superior gene transduction efficiency in both T cells and NK cells compared to feline endogenous retrovirus (RD114) pseudotyped retrovirus (RD114 RV) or vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentivirus (VSV-G LV). Among the various SRV pseudotypes tested, only the SRV2 RV successfully transduces genes into immune cells. Unlike the SRV2 RV, however, lentivirus pseudotyped with the SRV2 envelope glycoprotein (ENV) fails to mediate gene transduction into T cells. CAR-T and NK cells generated using SRV2 RV demonstrate substantial anticancer activity both in vitro and in preclinical models. In conclusion, our findings highlight the SRV2 RV as a highly effective platform for producing CAR-based immune cells.