Aminobisphosphonates as new weapons for γδ T cell-based immunotherapy of cancer

Several observations in mice and in humans have collectively laid the foundation for examining the potential of gamma delta T cells to exert tumor immunotherapy. Human gamma delta T cells can be activated in a non-MHC dependent fashion either by low molecular mass phosphoantigens, or by agents that provoke the accumulation of endogenous pyrophosphates such as isopentenylpyrophosphate. Among the latter, aminobisphosphonates are well-established in the clinic, and extensive data are available on the compounds' antiangiogenic, antiosteolytic and pro-apoptotic properties. In this review we discuss on the possibility that the intentional activation of gamma delta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in patients with different types of cancer.