Zoledronate-activated Vγ9γδ T cell-based immunotherapy is feasible and restores the impairment of γδ T cells in patients with solid tumors.
Gamma/delta (γδ) T cells play a role in innate immunity and exhibit cytotoxicity toward a large range of tumor types. Recent studies have shown that aminobisphosphonates may be applied to a culture in which a large number of γδ T cells are proliferated ex vivo. We carried out a clinical study of 25 patients with various solid tumors to determine further the safety, immunologic effect and feasibility of zoledronate-activated Vγ9γδ T cell-based immunotherapy. No severe toxicity was observed. In the cells used for the first treatment, the total cell number, frequency and number of CD3(+) Vγ9(+) γδ T cells were 409 ± 284 × 10(7) cells, 56 ± 33% and 255 ± 242 × 10(7) cells, respectively. Aminobisphosphonate therapy or chemotherapy resulted in the suppression of CD3(+) Vγ9(+) γδ T-cell proliferation. The numbers of CD3(+) T cells, CD3(+) Vγ9(+) γδ T cells and CD27(-) CD45RA(-) Vγ9(+) subsets in peripheral blood were significantly lower in patients than in healthy subjects (P < 0.05). From such an impaired immunologic condition, the numbers and frequencies of CD3(+) Vγ9(+) γδ T cells and CD27(-) CD45RA(-) subsets significantly increased in patients treated with this immunotherapy. Zoledronate-activated Vγ9γδ T cell-based immunotherapy that restores the number of Vγ9γδ T cells in cancer patients may provide another mode of adoptive immunotherapy.
Noguchi
Atsutaka
A
Seta Clinic Group, Seta Clinic Tokyo, 3-6-5 Iidabashi, Chiyoda-ku, Tokyo, Japan.
Kaneko
Toru
T
Kamigaki
Takashi
T
Fujimoto
Katsunada
K
Ozawa
Masanori
M
Saito
Masashi
M
Ariyoshi
Naoko
N
Goto
Shigenori
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521522:T-cell receptor Vgamma9, human; D000077211:Zoledronic Acid