title: Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain and the common γ-chain.
abstract: OBJECTIVE
  Adoptive immunotherapy is emerging as a potent anti-tumor treatment modality; Vγ9Vδ2 T cells may represent appropriate agents for such cancer immunotherapy. To improve the currently limited success of Vγ9Vδ2 T-cell-based immunotherapy, we examined the in vivo dynamics of these adoptively-transferred cells and hypothesized that interleukin (IL)-15 is the potential factor for Vγ9δ2 T cell in vivo survival.
  
  
  METHODS
  We conducted a clinical trial of adoptive Vγ9Vδ2 T-cell transfer therapy in six colorectal cancer patients who received pulmonary metastasectomy. Patients' peripheral blood mononuclear cells were stimulated with zoledronate (5 μmol/L) and IL-2 (1000 IU/mL) for 14 d. Harvested cells, mostly Vγ9Vδ2 T cells, were given intravenously weekly without additional IL-2 eight times in total. The frequency, phenotype and common γ-chain cytokine receptor expression of Vγ9Vδ2 T cells in peripheral blood was monitored by flow cytometry at each time point during treatment and 4 and 12 weeks after the last administration.
  
  
  RESULTS
  Adoptively transferred Vγ9Vδ2 T cells expanded well without exogenous IL-2 administration or lymphodepleting preconditioning. They maintained effector functions in terms of interferon-γ secretion and prompt release of cytotoxic granules in response to PMA/ionomycin or isopentenyl pyrophosphate-positive cells. Because they are IL-2Rα(-)IL-7Rα(-)IL-15Rα(-)IL-2Rβ(+)γc(+), it is likely that IL-2 or IL-15 is required for their maintenance.
  
  
  CONCLUSIONS
  The persistence of large numbers of functionally active adoptively transferred Vγ9Vδ2 T cells in the absence of exogenous IL-2 implies that an endogenous factor, such as IL-15 transpresentation, is adequate to support these cells in vivo.
authors: Department of Immunotherapeutics, the University of Tokyo Hospital, Tokyo, Japan.
authors: Takamichi
authors: T
authors: Izumi
authors: Makoto
authors: M
authors: Kondo
authors: Takuya
authors: T
authors: Takahashi
authors: Nao
authors: N
authors: Fujieda
authors: Atsushi
authors: A
authors: Kondo
authors: Naohisa
authors: N
authors: Tamura
authors: Tomohiro
authors: T
authors: Murakawa
authors: Jun
authors: J
authors: Nakajima
authors: Hirokazu
authors: H
authors: Matsushita
authors: Kazuhiro
authors: K
authors: Kakimi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D004164:Diphosphonates / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D053631:Interleukin Receptor Common gamma Subunit / Q000096:biosynthesis / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid