Vγ9+ γδ T cells of glioblastoma multiforme (GBM) patients expanded ex vivo kill GBM cell lines and secrete IFNγ in vitro, suggesting their therapeutic potential. (P2108)

Abstract

Abstract 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.