133 : In vitro eradication of serous ovarian cancer with IFN-α2α and IFN-γ in combination with monocytes

Interferons (IFNs) have been utilized for their antiproliferative and antitumor effects against human cancers, including hairy cell leukemia, chronic myelogenous leukemia, and malignant melanoma. We have previously shown that in combination with human elutriation-purified monocytes, IFN- α 2a and IFN- γ have nearly eradicated certain cancer cell types in vitro and in vivo in a nude mouse model. More specifically, previous in vitro studies have shown the eradication of human osteosarcoma, LOX melanoma, and A549 lung tumor cells, while no such effect seen on the human diploid cell lines WI-38 and MRC-5. Further in vivo analysis of OVCAR-3 and LOX melanoma inoculated intratumorally in female BALB/c nude mice showed that combination therapy significantly reduced tumor growth more profoundly than IFNs or monocytes alone. Such finding may have clinical implications. We have adapted this IFN and monocyte combination treatment model towards human serous ovarian cancer, a subtype accounting for approximately 60–80% of ovarian cancer diagnoses. We further validated IFN-primed monocytes as a novel antitumor treatment against ovarian tumor cells in vitro . Combination treatment has antitumor and antiproliferative effects towards the ovarian cancer cell lines SKOV-3, CaOV3, OVCAR-4, OVCAR-5, and OVCAR-8. These serous tumor cell lines show varying, though prevalent, anti-tumor and anti-proliferative effects following IFN-primed monocyte treatment. SKOV-3, OVCAR-4, and OVCAR-8 cells are moderately sensitive to treatment; however, CaOV3 and OVCAR-5 cells are highly sensitive, with near complete eradication. Results demonstrate that such treatment is a novel candidate for ovarian cancer. Future studies will include in vivo IFN-primed monocyte treatment of intraperitoneal xenografts of serous ovarian cancer cell lines in female BALB/c nude mice, treatment of tumor cells with IFN-primed monocytes in combination with cancer therapeutics, and treatment of ovarian cancer cells with IFN-primed monocytes extracted from patients diagnosed with ovarian cancer.