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

## TL;DR

This paper introduces a new lentiviral vector that can target and engineer T cells directly in the body, potentially simplifying and improving CAR-T cell therapy.

## Contribution

The novel contribution is a T cell-specific lentiviral vector that enables in vivo CAR-T cell generation without ex vivo activation.

## Key findings

- The engineered lentiviral vector specifically targets T cells without affecting other immune cells.
- The vector successfully delivers a CD19-targeting CAR molecule to primary T cells in vivo.
- In vivo generated CD19-CAR-T cells effectively clear B cell lymphoma.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-17342-1.