A targeting lentiviral vector for generation of CAR-T cells in vivo

Abstract Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable therapeutic efficacy in treating cancer and autoimmune diseases. However, current CAR-T cell therapy requires ex vivo T cell engineering, which is both time-consuming and cost-prohibitive, adding complexity to the overall treatment. In this study, using an engineered Sindbis virus envelope, we developed a lentiviral vector system with high specificity for targeting human T cell line and primary T cells, but not targeting other immune cell subsets. Notably, this T cell-specific lentiviral vector does not require additional anti-CD3/CD28 stimulation for primary T cell activation during infection in vitro. Furthermore, the lentiviral vector successfully delivered a CD19-targeting CAR molecule to human primary T cells in vivo. The in vivo generated CD19-CAR-T cells efficiently mediated B cell lymphoma clearance. Overall, our study provides a promising tool for the development of in vivo T cell engineering approaches.