Introduction: Ovarian cancer is a malignant tumor with a poor prognosis because it is asymptomatic and often discovered with an accumulation of ascites. Thus, the development of new treatments is needed. Gamma delta T cells have attracted attention as effectors of adoptive cell immunotherapy. To evaluate their safety, the intraperitoneal injection of in vitro-expanded gamma delta T cells with zoledronate was evaluated for the treatment of malignant ascites in ovarian cancer.
Methods: Seven patients were enrolled in this study from September 2014 to July 2017. All patients had malignant ascites and histologically diagnosed ovarian and primary peritoneal cancer. The primary outcome was the safety of an intraperitoneal injection of expanded gamma delta T cells. Patients underwent leukapheresis to harvest peripheral blood mononuclear cells, which were stimulated with 2-methyl-3-butenyl-1-pyrophosphate and interleukin-2, and cultured for 14 days. The patients then received expanded gamma delta T cells with zoledronate intraperitoneally through a catheter. In addition, all of the patients underwent standard therapy (operation or chemotherapy or bevacizumab or olaparib).
Results: The adverse events were grade 3 lymphopenia and grade 3 hypophosphatemia, which showed spontaneous recovery. These symptoms were considered an effect of zoledronate intraperitoneal injection.
Conclusions: Intraperitoneal injection of in vitro-expanded gamma delta T cells with zoledronate was tolerated for malignant ascites in ovarian or primary peritoneal cancer.
The study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) on September 11, 2014 (Unique Trial Number: UMIN000015233)