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

Abstract

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 < 0.05). From such an impaired immunologic condition, the numbers and frequencies of CD3⁺ Vγ9⁺ γδ T cells and CD27⁻ CD45RA⁻ subsets significantly increased in patients treated with this immunotherapy. Zoledronate-activated Vγ9γδ T cell-based immunotherapy that restores the number of Vγ9γδ T cells in cancer patients may provide another mode of adoptive immunotherapy.

Key words::

• adoptive immunotherapy
• cancer
• γδ T cells
• Vγ9γδ T cells
• zoledronate

Disclosure of interest: The authors have no financial conflict of interest.