Publikationsdatenbank

ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Weber, Justus

Rade, Michael

Michael, Josefine

Tony, Liz Therese

Freitag, Fabian

Spieler, Peter

Müller, Claudia

Kalogirou, Charis

Mainz, Laura

Lehmann, Jörg

Klopfleisch, Robert (WE 12)

Rosenfeldt, Mathias T.

Danhof, Sophia

Kortüm, K. Martin

Köhl, Ulrike

Einsele, Hermann

Rader, Christoph

Reiche, Kristin

Nerreter, Thomas

Hudecek, Michael

Quelle

Cell reports : Medicine

Bandzählung: AOP

Seiten: 102400

ISSN: 2666-3791

Sprache

Englisch

Verweise

URL (Volltext): https://linkinghub.elsevier.com/retrieve/pii/S2666379125004732

DOI: 10.1016/j.xcrm.2025.102400

Pubmed: 41056951

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Receptor tyrosine kinase (RTK)-like orphan receptor 2 (ROR2) has been nominated as a target for kinase inhibitors due to its role in oncogenic signaling. Here, we show that ROR2 is a target for chimeric antigen receptor (CAR) T cells in hematologic and solid tumors. We show consistent ROR2 expression in multiple myeloma (MM) and developed ROR2-CAR T cells that confer potent activity against human MM xenografts in vivo. We analyzed public gene expression data and reveal an inverse correlation between ROR2 expression and patient survival for six types of cancer, i.e., lower-grade glioma, thyroid carcinoma, stomach adenocarcinoma, bladder cancer, and papillary and clear cell renal cell cancer (ccRCC). We confirm potent activity of ROR2-CAR T cells against ccRCC in vitro and in vivo. Treatment with ROR2-CAR T cells was well tolerated, without signs of on-target off-tumor toxicity in mice, supporting the role of ROR2 as an oncofetal antigen with utility for CAR T cell therapy.