title: Intraperitoneal injection of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer.
abstract: Malignant ascites caused by peritoneal dissemination of gastric cancer is chemotherapy-resistant and associated with poor prognosis. We conducted a pilot study to evaluate the safety of weekly intraperitoneal injections of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of such malignant ascites. Patient peripheral blood mononuclear cells were stimulated with zoledronate (5 μmol/L) and interleukin-2 (1000 IU/mL). After 14 days culture, Vγ9Vδ2 T-cells were harvested and administered intraperitoneally in four weekly infusions. The day before T-cell injection, patients received zoledronate (1 mg) to sensitize their tumor cells to Vγ9Vδ2 T-cell recognition. Seven patients were enrolled in this study. The number of Vγ9Vδ2 T-cells in each injection ranged from 0.6 to 69.8 × 10(8) (median 59.0 × 10(8)). There were no severe adverse events related to the therapy. Intraperitoneal injection of Vγ9Vδ2 T cells allows them access to the tumor cells in the peritoneal cavity. The number of tumor cells in the ascites was significantly reduced even after the first round of therapy and remained substantially lower over the course of treatment. IFN-γ was detected in the ascites on treatment. Computed tomography revealed a significant reduction in volume of ascites in two of seven patients. Thus, injection of these antitumor Vγ9Vδ2 T-cells can result in local control of malignant ascites in patients for whom no standard therapy apart from paracentesis is available. Adoptively transferred Vγ9Vδ2 T-cells do indeed recognize tumor cells and exert antitumor effector activity in vivo, when they access to the tumor cells.
authors: Department of Gastrointestinal Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors: Ikuo
authors: I
authors: Wada
authors: Hirokazu
authors: H
authors: Matsushita
authors: Shuichi
authors: S
authors: Noji
authors: Kazuhiko
authors: K
authors: Mori
authors: Hiroharu
authors: H
authors: Yamashita
authors: Sachiyo
authors: S
authors: Nomura
authors: Nobuyuki
authors: N
authors: Shimizu
authors: Yasuyuki
authors: Y
authors: Seto
authors: Kazuhiro
authors: K
authors: Kakimi
mesh_terms: D000328:Adult; D000368:Aged; D001201:Ascites / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive / Q000379:methods; D007274:Injections, Intraperitoneal; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; D000077211:Zoledronic Acid
keywords: Gastric cancer; Vγ9Vδ2 T-cell; malignant ascites; peritoneal dissemination; zoledronate