# DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors

## TL;DR

This study shows that CAR-T cells targeting DSG2 can safely and effectively eliminate various solid tumors in mice.

## Contribution

The study introduces DSG2 as a novel, universally expressed target for CAR-T therapy in solid tumors.

## Key findings

- DSG2-directed CAR-T cells effectively eliminate multiple solid tumor types in vivo.
- Administration of αDSG2 CAR-T cells to transgenic mice caused no toxicity.
- DSG2 is a junctionally-restricted antigen suitable for targeting solid tumors.

## Abstract

CAR-T cell therapies are curative for advanced hematologic cancers, however that potential has yet to be realized in epithelia-derived solid tumors reflecting the limited portfolio of cancer-restricted, cell-surface targets. Desmoglein 2 (DSG2) is a desmosomal cadherin universally overexpressed on the surface of transformed epithelial cells, with normal protein expression believed to be junctionally-restricted between adjacent cells, creating a “window of opportunity” to eliminate solid tumors without toxicity. Here, we generated DSG2-directed CAR-T cells (αDSG2) that universally recognize and lyse assorted solid tumor cell lines in vitro and eliminated patient-derived and cell-derived colon, pancreatic, lung, prostate, breast, and liver tumors in vivo. Transgenic mice expressing human DSG2 experienced no toxicity following αDSG2 CAR-T cell administration. These studies reveal safe and robust antitumor activity of αDSG2 CAR-T cells and introduce a new class of junctionally-restricted antigens that can be safely and effectively targeted across solid tumor types.