ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice
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.
Authors
- Charis Kalogirou (ORCID: https://orcid.org/0000-0003-3802-940X)
- Robert Klopfleisch (ORCID: https://orcid.org/0000-0002-6308-0568)
- Thomas Nerreter (ORCID: https://orcid.org/0000-0002-0493-1369)
- Michael Rade (ORCID: https://orcid.org/0000-0001-6247-9289)
- Ulrike Koehl (ORCID: https://orcid.org/0000-0002-8159-9160)
- Kristin Reiche (ORCID: https://orcid.org/0000-0002-4452-4872)
- Sophia Danhof (ORCID: https://orcid.org/0000-0003-1316-0241)
- Jörg Lehmann (ORCID: https://orcid.org/0000-0001-8560-648X)
- Fabian Freitag (ORCID: https://orcid.org/0000-0002-6656-6192)
- Christoph Rader
- K. Martin Kortüm (ORCID: https://orcid.org/0000-0002-7011-0286)
- Justus Weber (ORCID: https://orcid.org/0000-0002-4919-952X)
- Laura Mainz (ORCID: https://orcid.org/0000-0002-3986-7547)
- Josefine Michael
- Mathias T. Rosenfeldt (ORCID: https://orcid.org/0000-0001-7650-8458)
- Hermann Einsele
- Liz Therese Tony
- Claudia Mueller (ORCID: https://orcid.org/0000-0003-2670-5626)
- Peter Spieler (ORCID: https://orcid.org/0009-0000-2109-6169)
- Michael Hudecek
Institutions
- Scripps Research Institute (US)
- University of Würzburg (DE)
- Universitätsklinikum Würzburg (DE)
- Fraunhofer Institute for Cell Therapy and Immunology (DE)
- Freie Universität Berlin (DE)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102400
- Citations
- 1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.05