Zoledronate-activated Vγ9γδ T cell-based immunotherapy is feasible and restores the impairment of γδ T cells in patients with solid tumors

Gamma/delta (γδ) T cells play a role in innate immunity and exhibit cytotoxicity toward a large range of tumor types. Recent studies have shown that aminobisphosphonates may be applied to a culture in which a large number of γδ T cells are proliferated ex vivo. We carried out a clinical study of 25 patients with various solid tumors to determine further the safety, immunologic effect and feasibility of zoledronate-activated Vγ9γδ T cell-based immunotherapy. No severe toxicity was observed. In the cells used for the first treatment, the total cell number, frequency and number of CD3+ Vγ9+ γδ T cells were 409 ± 284 × 107 cells, 56 ± 33% and 255 ± 242 × 107 cells, respectively. Aminobisphosphonate therapy or chemotherapy resulted in the suppression of CD3+ Vγ9+ γδ T-cell proliferation. The numbers of CD3+ T cells, CD3+ Vγ9+ γδ T cells and CD27− CD45RA− Vγ9+ subsets in peripheral blood were significantly lower in patients than in healthy subjects (P