Aminobisphosphonate-activated γδ T cells in immunotherapy of cancer: doubts no more

Abstract

Background: Activated Vγ9Vδ2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. Objective: We discuss the possibility that the intentional activation of γδ T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. Methods: The antitumoural effects of γδ T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. Results/conclusion: Vγ9Vδ2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-aminobisphosphonate administration and several Phase I-II trials are ongoing investigating the activity of zoledronic acid plus IL-2 in solid tumours.

Keywords::

• bisphosphonates
• cytokines
• cytotoxicity
• human γδ
• immunomodulation
• memory-phenotype
• T cells, tumours

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