Application of CAR-T cell therapy in orthopedics: From bone malignancies to non-malignant musculoskeletal disorders.
5 affiliations
- 1The Affiliated Hospital of Wuhan Sports University, Wuhan, China.
- 2XiangNan University, Chenzhou City, Hunan Province, China.
- 3Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
- 4Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
- 5Hubei University of Chinese Medicine, Wuhan, China.
Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed hematologic oncology, but its application in orthopaedic diseases remains at an early stage. In bone malignancies, including osteosarcoma, chondrosarcoma, Ewing sarcoma, and bone metastases, antigen heterogeneity, limited trafficking and persistence, and the immunosuppressive skeletal microenvironment restrict efficacy. CAR-engineered approaches are also emerging in non-malignant disorders: CD19-directed CAR-T therapy has shown early clinical activity in refractory rheumatoid arthritis and other autoimmune rheumatic diseases, whereas senolytic CAR-T strategies for osteoarthritis remain preclinical. This review summarizes current evidence across malignant and non-malignant orthopaedic conditions, with emphasis on target selection, safety, and translational feasibility. Key barriers include antigen escape, impaired infiltration, limited persistence, local immunosuppression, manufacturing complexity, and on-target/off-tumour toxicity. Emerging strategies include multi-target receptors, chemokine receptor engineering, locoregional delivery, safety-control systems, and allogeneic or point-of-care manufacturing. Current evidence supports CAR-T and related CAR-engineered cells as potential complementary approaches for selected refractory orthopaedic conditions, although further translation requires stronger clinical evidence and improved biological and manufacturing strategies. The Translational Potential of this Article: This review identifies disease-specific targets, barriers, and engineering priorities relevant to translating CAR-engineered cell therapies into orthopaedic practice. These considerations may inform preclinical validation and early-phase trials in refractory bone malignancies and selected non-malignant musculoskeletal disorders.
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BibTeX
@article{que2026application,
title = {{Application of CAR-T cell therapy in orthopedics: From bone malignancies to non-malignant musculoskeletal disorders.}},
author = {Yimei Que and Xienilai Xie and Wei Xie and Yunzhou Zuo and Wang Chen and Zedong Xu and Changtian Gong and Xugui Li},
journal = {Journal of orthopaedic translation},
year = {2026},
month = oct,
doi = {10.1016/j.jot.2026.101235},
url = {https://europepmc.org/article/MED/42898659},
note = {CC BY},
}
RIS
TY - JOUR
TI - Application of CAR-T cell therapy in orthopedics: From bone malignancies to non-malignant musculoskeletal disorders.
AU - Yimei Que
AU - Xienilai Xie
AU - Wei Xie
AU - Yunzhou Zuo
AU - Wang Chen
AU - Zedong Xu
AU - Changtian Gong
AU - Xugui Li
PY - 2026
DA - 2026/10/10
JO - Journal of orthopaedic translation
DO - 10.1016/j.jot.2026.101235
UR - https://europepmc.org/article/MED/42898659
AB - Chimeric antigen receptor T-cell (CAR-T) therapy has transformed hematologic oncology, but its application in orthopaedic diseases remains at an early stage. In bone malignancies, including osteosarcoma, chondrosarcoma, Ewing sarcoma, and bone metastases, antigen heterogeneity, limited trafficking and persistence, and the immunosuppressive skeletal microenvironment restrict efficacy. CAR-engineered approaches are also emerging in non-malignant disorders: CD19-directed CAR-T therapy has shown early clinical activity in refractory rheumatoid arthritis and other autoimmune rheumatic diseases, whereas senolytic CAR-T strategies for osteoarthritis remain preclinical. This review summarizes current evidence across malignant and non-malignant orthopaedic conditions, with emphasis on target selection, safety, and translational feasibility. Key barriers include antigen escape, impaired infiltration, limited persistence, local immunosuppression, manufacturing complexity, and on-target/off-tumour toxicity. Emerging strategies include multi-target receptors, chemokine receptor engineering, locoregional delivery, safety-control systems, and allogeneic or point-of-care manufacturing. Current evidence supports CAR-T and related CAR-engineered cells as potential complementary approaches for selected refractory orthopaedic conditions, although further translation requires stronger clinical evidence and improved biological and manufacturing strategies. The Translational Potential of this Article: This review identifies disease-specific targets, barriers, and engineering priorities relevant to translating CAR-engineered cell therapies into orthopaedic practice. These considerations may inform preclinical validation and early-phase trials in refractory bone malignancies and selected non-malignant musculoskeletal disorders.
SN - 2214-031X
SN - 2214-0328
ER -