Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours

BACKGROUND: Adoptive transfer of ex vivo expanded autologous V gamma 9V delta 2 T cells may be of therapeutic benefit for cancer because of their potent direct cytotoxicity towards tumour cells, synergistic cytotoxicity when combined with aminobisphosphonates and enhancement of antibody-dependent cell-mediated cytotoxicity. METHODS: To determine the feasibility and clinical safety of therapy with ex vivo expanded, activated V gamma 9V delta 2 T cells in combination with zoledronate, we enrolled 18 subjects with advanced solid tumours into a phase I clinical study. Administered indium(111)-oxine-labelled V gamma 9V delta 2T cells were tracked in a cohort of patients. RESULTS: Administered V gamma 9V delta 2 T cells had an activated effector memory phenotype, expressed chemokine receptors predictive of homing to peripheral tissues and were cytotoxic in vitro against tumour targets. Adoptively transferred V gamma 9V delta 2 T cells trafficked predominantly to the lungs, liver and spleen and, in some patients, to metastatic tumour sites outside these organs. No dose-limiting toxicity was observed, but most patients progressed on study therapy. However, three patients administered V gamma 9V delta 2 T cells while continuing previously ineffective therapy had disease responses, suggesting an additive effect. CONCLUSION: Therapy with aminobisphosphonate-activated V gamma 9V delta 2 T cells is feasible and well tolerated, but therapeutic benefits appear only likely when used in combination with other therapies. British Journal of Cancer (2011) 105, 778-786. doi: 10.1038/bjc.2011.293 www.bjcancer.com Published online 16 August 2011 (C) 2011 Cancer Research UK