Development of a minimal residual disease ovarian cancer model in immunocompetent mice

Abstract

16590 Background: To develop an immunocompetent mouse ovarian cancer model in immunocompetent mice. Methods: Clonal cell lines of mouse ovarian surface epithelial cells (MOSEC) were transfected with firefly luciferase. After FACS analysis, luciferase stably-transfected MOSEC were injected intraperitoneally into C57/BL6 mice using various titrations of MOSEC. Tumors were visualized using a bioluminescence imaging system and measured using hematoxylin and eosin staining. Survival analyses were calculated using Kaplan-Meier analysis. Results: In vitro bioluminescence of MOSEC gfp-luc cells were visualized with as low as 976 cells. Mice injected intraperitoneally with 0.1, 1.0, and 5.0 × 106 MOSEC gfp-luc demonstrated increasing levels of bioluminescence with corresponding median survivals of 95, 112, and 124 days, respectively (p<0.001). Immunocompetent C57/BL6 mice that underwent sublethal radiation had increased tumor burden and rapid tumor progression compared to those without radiation. At early-stage disease, microscopic tumor implants were visualized and resected using bioluminescence imaging. On ex vivo resection, tumors were found to have microscopic disease during surgical dissection. On ex vivo imaging, these tumors which were located on the ovary, liver, and small bowel mesentery, had average measurements of 50–100 microns. Tumor implantation, growth, and metastases closely resembled that of human ovarian cancer with hemorrhagic ascites, omental caking, intestinal obstruction, and large pelvic tumors. Conclusions: This immunocompetent mouse model of ovarian cancer with minimal residual disease state closely resembles that of human ovarian cancer. Using this sygeneic cancer model, we are now able to study the effects of biologic therapy in an immunocompetent system. No significant financial relationships to disclose.