RRC ID 71747
著者 Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K.
タイトル 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.
ジャーナル Cytotherapy
Abstract BACKGROUND AIMS: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.
巻・号 15(4)
ページ 481-91
公開日 2013-4-1
DOI 10.1016/j.jcyt.2012.12.004
PII S1465-3249(12)00101-6
PMID 23391461
MeSH Aged Aged, 80 and over Cell Proliferation Colorectal Neoplasms / immunology Colorectal Neoplasms / therapy* Diphosphonates / pharmacology Female Humans Imidazoles / pharmacology Immunotherapy, Adoptive / methods* Interleukin Receptor Common gamma Subunit / biosynthesis Interleukin Receptor Common gamma Subunit / immunology* Interleukin-15 / immunology Interleukin-2 / pharmacology Interleukin-2 Receptor beta Subunit / biosynthesis Interleukin-2 Receptor beta Subunit / immunology* Leukocytes, Mononuclear / drug effects Lymphocyte Activation Male Middle Aged Receptors, Antigen, T-Cell, gamma-delta / immunology* Receptors, Antigen, T-Cell, gamma-delta / metabolism T-Lymphocyte Subsets / immunology* T-Lymphocyte Subsets / metabolism T-Lymphocyte Subsets / transplantation* Zoledronic Acid
IF 4.218
リソース情報
ヒト・動物細胞 DAUDI(RCB1640)