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

2011; Springer Nature; Volume: 105; Issue: 6 Linguagem: Inglês

10.1038/bjc.2011.293

1532-1827

Andrew J. Nicol, Hirotake Tokuyama, Stephen R. Mattarollo, Tomomi Hagi, Kenshi Suzuki, Kiyoshi Yokokawa, Mie Nieda,

T-cell and B-cell Immunology

Adoptive transfer of ex vivo expanded autologous Vγ9Vδ2 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. To determine the feasibility and clinical safety of therapy with ex vivo expanded, activated Vγ9Vδ2 T cells in combination with zoledronate, we enrolled 18 subjects with advanced solid tumours into a phase I clinical study. Administered indium111-oxine-labelled Vγ9Vδ2 T cells were tracked in a cohort of patients. Administered Vγ9Vδ2 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 Vγ9Vδ2 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 Vγ9Vδ2 T cells while continuing previously ineffective therapy had disease responses, suggesting an additive effect. Therapy with aminobisphosphonate-activated Vγ9Vδ2 T cells is feasible and well tolerated, but therapeutic benefits appear only likely when used in combination with other therapies.