Intraperitoneal injection of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer

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 Vc gamma Vd delta T cells together with zoledronate for the treatment of such malignant ascites. Patient peripheral blood mononuclear cells were stimulated with zoledronate (5 mu mol/L) and interleukin-2 (1000 IU/mL). After 14 days culture, Vc gamma Vd delta 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 Vc gamma Vd delta T-cell recognition. Seven patients were enrolled in this study. The number of Vc gamma Vd delta T-cells in each injection ranged from 0.6 to 69.8 x 10(8) (median 59.0 x 10(8)). There were no severe adverse events related to the therapy. Intraperitoneal injection of Vc gamma Vd delta 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-gamma 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 Vc gamma Vd delta T-cells can result in local control of malignant ascites in patients for whom no standard therapy apart from paracentesis is available. Adoptively transferred Vc gamma Vd delta T-cells do indeed recognize tumor cells and exert antitumor effector activity in vivo, when they access to the tumor cells.