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B7-H3-CAR T cells is an investigational autologous chimeric antigen receptor (CAR) T-cell therapy developed by St. Jude Children's Research Hospital for the treatment of pediatric patients with relapsed or refractory B7-H3-positive sarcomas. The therapy involves genetically engineering a patient's own T cells to express a CAR targeting B7-H3 (CD276), a checkpoint molecule that is highly expressed on various pediatric solid tumors, including osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma, while maintaining limited expression in normal tissues. The specific CAR construct utilizes a single-chain variable fragment (scFv) derived from the MGA271 (enoblituzumab) antibody and incorporates both CD28 and 4-1BB costimulatory domains to enhance T-cell activation, metabolic fitness, and long-term persistence. In clinical trials, such as the RAD3CAR study, the therapy is evaluated in combination with hypofractionated radiation therapy and lymphodepleting chemotherapy (fludarabine and cyclophosphamide) to potentially improve CAR T-cell trafficking and overcome the immunosuppressive tumor microenvironment.
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