DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors.
Publication/Presentation Date
2-12-2026
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.
ISSN
2693-5015
Published In/Presented At
Snook, A., Carlson, R., Weil, L., Baybutt, T., Kulak, O., Cao, M., Staudt, R., Jain, P., Crutcher, M., Entezari, A., Caspi, A., Kopenhaver, J., Londregan, A., Barton, J., Kuret, T., Gandhi, V., Habash, E., Wahl, J., Lieber, A., Waldman, S., … Mahoney, M. (2026). DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors. Research square, rs.3.rs-5909002. https://doi.org/10.21203/rs.3.rs-5909002/v1
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
41727586
Department(s)
Administration and Leadership
Document Type
Article