Sensitization of human osteosarcoma cells to Vγ9Vδ2 T-cell-mediated cytotoxicity by zoledronate

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 V?9Vd2 T lymphocytes represents an attractive strategy. We have investigated combining adoptive immunotherapy with V?9Vd2 T cells and zoledronate to optimize osteosarcoma therapy. V?9Vd2 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 V?9Vd2 T cells may be an effective complement to current chemotherapies. (c) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:824830, 2012