Authors
Adam Snook, Robert Carlson, Lindsay Weil, Trevor Baybutt, Ozlem Kulak, Miao Cao, Ross Staudt, Pranav Jain, Madison Crutcher, Ariana Entezari, Adi Caspi, Jessica Kopenhaver, Annie Londregan, Joshua Barton, Thomas Kuret, Vishwa Gandhi, Elizabeth Habash, James Wahl, André Lieber, Scott Waldman, My Mahoney
Published in
Research square. Feb 12, 2026. Epub Feb 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.
PMID:
41727586
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.
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