Mechanisms of Antitumor Action of Human Interferon

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We have now shown that co-culture of Interferon alpha and gamma primed monocytes are capable of killing ovarian tumor cells both in vitro and in vivo, and the presence of both interferons is necessary for the tumorcidal effect. Further, we have shown that monocytes primed with alpha and gamma interferon combined with the standard chemotherapeutic agents Taxol and Carboplatin results in increased killing of target tumor cells. We have shown that 10 ovarian cancer cell lines are sensitive to this treatment regimen. Furthermore, we have extended this observation to show that monocytes isolated from the whole blood of healthy donors are capable of killing cells in vitro. We have also performed an advanced microarray analysis of monocytes treated with the interferons to identify which protein(s) are mediating the in vivo cell death. The array has identified a number of target genes for validation and further study. We have been isolating monocytes from patients with ovarian cancer in collaboration with Dr. Annunziata. We have found that patient monocytes are as effective killers of ovarian cancer cell lines as healthy human age matched controls.