RRC ID 44906
Author Wada I, Matsushita H, Noji S, Mori K, Yamashita H, Nomura S, Shimizu N, Seto Y, Kakimi K.
Title Intraperitoneal injection of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer.
Journal Cancer Med
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.
Volume 3(2)
Pages 362-75
Published 2014-4-1
DOI 10.1002/cam4.196
PMID 24515916
PMC PMC3987085
MeSH Adult Aged Ascites / immunology Ascites / pathology Ascites / therapy* Bone Density Conservation Agents / therapeutic use Diphosphonates / therapeutic use* Female Humans Imidazoles / therapeutic use* Immunotherapy, Adoptive / methods Injections, Intraperitoneal Male Middle Aged Pilot Projects Receptors, Antigen, T-Cell, gamma-delta / immunology* Stomach Neoplasms / immunology Stomach Neoplasms / pathology* Stomach Neoplasms / therapy* T-Lymphocytes / immunology* Zoledronic Acid
IF 3.491
Times Cited 34
Human and Animal Cells DAUDI(RCB1640)