Abstract A52: Efficacy of specified natural killer (NK) cells in ovarian cancer xenograft models.

Objective: Natural killer (NK) cells are one of the most essential cell types, and they rank with cytotoxic T lymphocytes (CTLs) as regards strong cytotoxic activity against malignant tumor cells in the cellular immune response. Recent advances have led to the hope that NK cells could be harnessed as a therapy for cancers. Expanded specified NK cells show potent cytotoxic activity against tumor cells in vitro and in vivo. Recently, some evidence suggests that NK cells can help to control ovarian tumor growth has been provided by the analysis of tumor prevalence in immunodeficient mice. Therefore, we investigated whether expanded NK cells have potent cytotoxic activity against human ovarian cancer xenografts Methods: We have established a novel method for the expansion and activation of NK cells from healthy volunteers for allogeneic NK cell therapy. A highly pure population of CD16+CD56+ NK cells can be obtained with minimal contamination by T cells, B cells, or monocytes. The specified NK cells which were selected after in vitro experiment screening of candidates by Facscan analysis and OVCAR3-Luc cells were selected. For NK cells, its anti-tumor efficacy was confirmed in mice through experiments of autopsies. For in vivo screening of anti-cancer cell therapy, an experimental xenograft model using OVCAR3-Luc cells was established and optimized by optical imaging method considering time and degree of tumorigenesis. The injection of 5x106 OVCAR3-luc cells were turned out suitable for screening model, because of rapid saturation time of optical signal and survival period of mouse. Tumor luminescence was static until 4 weeks postimplantation, after which a steady increase was noted. In addition the mice were weighed and examined for abdominal distension during each imaging session. Results: In this experimental animal model, tumor was predominantly generated in peritoneal area and in about 10% mice a small number of tumor-mass was spread under the peritoneal area. Despite the detectable increase in tumor burden by bioluminescence, measurable changes in girth and weight were not seen until later in the study. At Day 60, specified NK cell treatment displayed effective inhibition of ovarian cancer growth, while negative control showed negligible anticancer effect. Total flux of NK cell was much lower than that of negative control, but significance was low (T-Test, p=0.092). Paclitaxel acts in different mechanism to NK cell, was used as a positive control and showed gentle inhibition of ovarian cancer growth. Notable change of body weights in the mice was not observed in any group, indicating severe toxicity did not occur in those mice. Conclusions: As the results, specified NK cells showed potent inhibition of ovarian cancer proliferation in the OVCAR3-Luc cancer model. Therefore, specified NK cell therapy, has been shown to be an important role in the control and cure of at least some ovarian cancer diseases. Citation Format: Young Jae Lee, Ha Young Lee, Yu Kyung Hwang, Kyung Jin Lee, Shin Wha Lee, Yong Man Kim. Efficacy of specified natural killer (NK) cells in ovarian cancer xenograft models. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A52.