title: Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Centre for Immune and Targeted Therapy, University of Queensland, Brisbane, 4120 Australia. anic9909@bigpond.net.au
authors.forename: A J
authors.initials: AJ
authors.lastname: Nicol
authors.forename: H
authors.initials: H
authors.lastname: Tokuyama
authors.forename: S R
authors.initials: SR
authors.lastname: Mattarollo
authors.forename: T
authors.initials: T
authors.lastname: Hagi
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Yokokawa
authors.forename: M
authors.initials: M
authors.lastname: Nieda
mesh_terms: D000368:Aged; D004164:Diphosphonates / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid