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Br J Cancer. 2011 Sep 6;105(6):778-86. doi: 10.1038/bjc.2011.293. Epub 2011 Aug 16.

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

Author information

  • 1Department of Medicine, Centre for Immune and Targeted Therapy, University of Queensland, Brisbane, 4120 Australia. anic9909@bigpond.net.au

Abstract

BACKGROUND:

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.

METHODS:

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 indium(111)-oxine-labelled Vγ9Vδ2 T cells were tracked in a cohort of patients.

RESULTS:

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.

CONCLUSION:

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.

PMID:
21847128
[PubMed - indexed for MEDLINE]
PMCID:
PMC3171009
Free PMC Article

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