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Updated: May 27, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Genetically modified T cells targeting interleukin-11 receptor α-chain kill human osteosarcoma cells and induce the
Gangxiong Huang1, Ling Yu1, Laurence Jn Cooper1
1Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Abstract:
The treatment of osteosarcoma pulmonary metastases remains a challenge. T cells genetically modified to express a chimeric antigen receptor (CAR), which recognizes a tumor-associated antigen, have shown activity against hematopoietic malignancies in clinical trials, but this requires the identification of a specific receptor on the tumor cell. In the current study, we found that interleukin (IL)-11Rα was selectively expressed on 14 of 16 osteosarcoma patients' lung metastases and four different human osteosarcoma cell lines, indicating that IL-11Rα may be a novel target for CAR-specific T-cell therapy. IL-11Rα expression was absent or low in normal organ tissues, with the exception of the gastrointestinal tract. IL-11Rα-CAR-specific T cells were obtained by non-viral gene transfer of Sleeping Beauty DNA plasmids and selectively expanded ex vivo using artificial antigen-presenting cells derived from IL-11Rα + K562 cells genetically modified to coexpress T-cell costimulatory molecules. IL-11Rα-CAR(+) T cells killed all four osteosarcoma cell lines in vitro; cytotoxicity correlated with the level of IL-11Rα expression on the tumor cells. Intravenous injection of IL-11Rα-CAR(+) T cells into mice resulted in the regression of osteosarcoma pulmonary metastases with no organ toxicity. Together, the data suggest that IL-11Rα-CAR T cells may represent a new therapy for patients with osteosarcoma pulmonary metastases.
Insights
Interleukin-11 receptor alpha (IL-11Rα) is a novel target for osteosarcoma. CAR T-cells targeting IL-11Rα effectively eliminated lung metastases in mice with no organ toxicity.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Osteosarcoma pulmonary metastases present a significant therapeutic challenge.
- Chimeric antigen receptor (CAR) T-cell therapy shows promise but requires specific tumor targets.
- Interleukin-11 receptor alpha (IL-11Rα) is a potential target for osteosarcoma.
Purpose of the Study:
- To investigate IL-11Rα as a target for CAR T-cell therapy in osteosarcoma.
- To evaluate the efficacy and safety of IL-11Rα-CAR T-cells against osteosarcoma lung metastases.
Main Methods:
- Identified IL-11Rα expression on osteosarcoma lung metastases and cell lines.
- Generated IL-11Rα-CAR T-cells using non-viral gene transfer and ex vivo expansion.
- Assessed in vitro cytotoxicity and in vivo efficacy in a mouse model of osteosarcoma pulmonary metastases.
Main Results:
- IL-11Rα was selectively expressed on osteosarcoma lung metastases and cell lines, with low expression in normal tissues.
- IL-11Rα-CAR T-cells demonstrated potent in vitro cytotoxicity against osteosarcoma cells.
- In vivo administration of IL-11Rα-CAR T-cells led to regression of pulmonary metastases without observable organ toxicity.
Conclusions:
- IL-11Rα is a promising novel target for CAR T-cell therapy in osteosarcoma.
- IL-11Rα-CAR T-cells offer a potential new therapeutic strategy for osteosarcoma pulmonary metastases.
- This approach warrants further investigation for clinical application.
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