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 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. A mouse toxicity study for the monocytes with and without the interferons (OSD31) showed that there was no toxicity based on no gross pathology or blood chemistries as determined by a registered pathologist. We have initiated the process to file an FDA IND (IND17040), and an IRB protocol is in its final stages of review for translation of our work into the clinic..We have also expanded our approaches to interferon based therapy with the combination of pseudomonas exotoxin-cytokine conjugates (IL4-PE) for the combination treatment of ovarian cancer with Dr. Raj Puri.The goal of this collaboration is to translate the observations that we have made into the clinic. Currently we are assessing the drug combination in a mouse model.
