Project Details

Advancing Pediatric Cancer Immunotherapy with CAR-NKT Cells

Andrew Wahba, MD

Summary

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and adolescents, yet outcomes for relapsed or refractory disease remain poor, with survival rates stagnating for decades despite intensive chemotherapy and surgery. GAP: Current immunotherapies, including CAR-T cells, have shown limited efficacy in pediatric solid tumors. HYPOTHESIS: We hypothesize that engineering invariant natural killer T (iNKT) cells to co-express a B7H3-targeted CAR and the cytokine IL-18 will enhance tumor killing and remodel the immunosuppressive microenvironment, resulting in superior anti-tumor activity compared to conventional CAR-T cells. METHODS: We will isolate and expand human iNKT cells from healthy donor peripheral blood and engineer them to express a B7H3-CAR and IL-18 using optimized viral transduction protocols. These engineered cells will undergo in-depth functional testing, including cytotoxicity assays, cytokine profiling, and multi-omic analyses using freshly resected pediatric osteosarcoma specimens. Efficacy and persistence will be evaluated in orthotopic and metastatic osteosarcoma mouse models that recapitulate human disease biology. RESULTS: Pending. IMPACT: This project aims to establish a next-generation immunotherapy platform for pediatric osteosarcoma by combining precise tumor targeting with microenvironment modulation.