GBM is the most common primary malignant brain tumor, carrying an ominous prognosis (< 2 years survival).Vγ9+ γδ (Vγ9+) T cells mediate major histocompatibility non restricted killing of tumor cells, suggesting Vγ9+ T cell- mediated adoptive immunotherapy may be of benefit in this disease. We established a protocol for ex-vivo expansion of Vγ9+ T cells from the peripheral blood (PB) of GBM patients, in whom Vγ9+ T cells consisted 0.55±0.58%(n=16) of the PB mononuclear cells (MC) just prior to surgical resection of the tumor (vs 0.91±0.42% in 9 healthy donors (HD), p<0.08). We found no correlation between % Vγ9+ T cells in patient PBMC and survival following surgical removal of the tumor. Nevertheless, short term culture of PBMC in the presence of a bisphosphonate, zoledronate (2μM) and 100 IU IL-2, expanded Vγ9+ T cells of all patients 522±466 fold, to consist 54±21% of the cultured MC (not significantly different from HD). The cultured cells were cytotoxic and expressed cytokines in response to GBM cell lines and autologous tumor derived cells. Furthermore, pre-treatment of the tumor with zoledronate, as well as with the clinical anti-GBM reagent temozolomide (TMZ), enhanced Vγ9+ T cell tumor recognition. These data suggest that adoptive immunotherapy employing autologously derived ex vivo activated and expanded Vγ9+T cells, in combination with zoledronate andTMZ, may lead to enhanced therapeutic responses in GBM patients.
- Copyright © 2013 by The American Association of Immunologists, Inc.