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Characterization of SKOV3-AF2 cells revealed that it is more susceptible to PBMC-mediated cytotoxicity than SKOV3-RFP and highly tumorigenic in a xenograph model, and AF-2 tumors express genes that promote aggressive behavior. Collectively, our data suggest that the SKOV3-AF2 subline will be a useful tool to test cellular therapy for the treatment of ovarian cancer utilizing experimental models.

Introduction: Because current therapies for ovarian cancer have little impact on the long-term survival, there is a compelling need to develop innovative strategies. Our aim was to functionally characterize a fluorescent highly tumorigenic ovarian cancer line to test cellular therapy in combination with cytokines or chemotherapies in experimental models. Methods: Two fluorescent highly tumorigenic sub-lines (SKOV3-AF1 and SKOV3-AF2) were derived from the SKOV-3 ovarian cancer cell line. Peripheral blood mononuclear cells (PBMC)-mediated cytotoxicity in combination with IL-2 and IFNα-2b of SKOV3-AF1 and -AF2 was assayed by lactate dehydrogenase release. Sensitivity of SKOV3-AF2 cells to polyethylene glycol (PEG)-IFNα-2b or IL-2 was assayed in a xenograph nude mouse model. Histopathology was performed on tumors harvested from mice to determine necrosis and tumor infiltrating lymphocytes in the solid tumors. Results: SKOV3-AF1 and -AF2 sub-lines exhibit increased cytotoxicity mediated by PBMC, IL-2, and IFNα-2b compared to parental SKOV-3 cells. The average cytotoxicity was 59% for both SKOV3-AF1 and -AF2 compared to 28% for SKOV-3 parental cells (p<0.05). SKOV3-AF1 and -AF2 cells are more tumorigenic in vivo compared to SKOV-3 cells as indicated by tumor incidence (SKOV3 66%, SKOV3-AF1 100%, SKOV3-AF2 100%), time to sacrifice, tumor weight, and ascitic fluid production. In addition, the SKOV3-AF2 cells continue to fluoresce when harvested from the mice. SKOV3-AF2 tumor growth was inhibited by PEG-IFNα-2b but not low-dose IL-2. The average tumor weight was 0.96 g in the control treatment group that did not receive PEG-IFNα-2b versus 0.23 g for PEG-IFNα-2b (12,000 U per week); p < 0.05). There was no significant difference in any of the IL-2 treatment groups (0-4,000 U, thrice weekly). Both PEG-IFNα-2b and IL-2 were well tolerated by the mice as demonstrated by no significant weight loss during the treatment. Histopathology revealed that the tumors consisted of poorly differentiated surface epithelial carcinoma and there was no significant difference in the percent necrosis or TIL score in any of the treatment groups. Conclusions: Characterization of SKOV3-AF2 cells revealed that these cells are more susceptible to PBMC-mediated cytotoxicity than SKOV-3 cells, are highly tumorigenic in a xenograph model, and continue to fluoresce when harvested from mice. Our data suggests that the SKOV3-AF2 sub-line will be a useful tool to test cellular therapy for the treatment of ovarian cancer utilizing experimental models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2708. doi:10.1158/1538-7445.AM2011-2708

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