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Despite improvements in the treatment of osteosarcoma, there is a need for new therapeutic strategies, in particular for the treatment of recurrent tumors and metastases. Adoptive immunotherapy with Vg9Vd2 T lymphocytes represents an attractive strategy. We have investigated combining adoptive immunotherapy with Vg9Vd2 T cells and zoledronate to optimize osteosarcoma therapy. Vg9Vd2 T cells, from healthy volunteers and patients with osteosarcoma, cultures alone demonstrated moderate or poor cytotoxic activity against osteosarcoma cell lines, respectively. The addition of zoledronate further increased cytotoxicity in vitro. This enhancement was largely dependent on the granule exocytose and partly on TRAIL pathways, was TCR-mediated and partly NKG2D-mediated. These data suggest that combined treatment of human osteosarcoma with zoledronate and Vg9Vd2 T cells may be an effective complement to current chemotherapies. ß

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