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Updated: Jan 15, 2026
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice
Justus Weber1, Michael Rade2, Josefine Michael1
1Chair for Cellular Immunotherapy, Department of Medicine II & Department of Medicine II, University Hospital Würzburg, Würzburg, Germany.
Abstract:
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.
Insights
Receptor tyrosine kinase-like orphan receptor 2 (ROR2) shows promise as a target for chimeric antigen receptor (CAR) T cell therapy in various cancers. ROR2-CAR T cells demonstrate potent anti-tumor activity with good tolerability in preclinical models.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Receptor tyrosine kinase (RTK)-like orphan receptor 2 (ROR2) is implicated in oncogenic signaling pathways.
- ROR2 has been identified as a potential target for therapeutic interventions in cancer treatment.
Purpose of the Study:
- To investigate the efficacy of chimeric antigen receptor (CAR) T cells targeting ROR2 in hematologic and solid tumors.
- To evaluate ROR2 expression patterns in various cancer types and correlate them with patient survival.
Main Methods:
- Development of ROR2-specific CAR T cells.
- In vitro and in vivo testing of ROR2-CAR T cells against multiple myeloma and clear cell renal cell carcinoma (ccRCC) models.
- Analysis of public gene expression datasets to assess ROR2 expression and its correlation with survival in six cancer types.
Main Results:
- Consistent ROR2 expression was observed in multiple myeloma.
- ROR2-CAR T cells exhibited potent anti-tumor activity against human multiple myeloma xenografts in vivo.
- An inverse correlation between ROR2 expression and patient survival was found in lower-grade glioma, thyroid carcinoma, stomach adenocarcinoma, bladder cancer, and ccRCC.
- ROR2-CAR T cells showed potent activity against ccRCC in vitro and in vivo.
- Treatment with ROR2-CAR T cells was well-tolerated in mice, with no observed on-target off-tumor toxicity.
Conclusions:
- ROR2 is a viable target for CAR T cell therapy in both hematologic and solid tumors.
- ROR2-CAR T cells demonstrate significant anti-cancer efficacy and a favorable safety profile in preclinical studies.
- ROR2 may function as an oncofetal antigen, highlighting its therapeutic potential for CAR T cell-based cancer treatments.
