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

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$214,340
Indirect Cost
City
State
Country
Zip Code
Green, Daniel S; Nunes, Ana T; Annunziata, Christina M et al. (2016) Monocyte and interferon based therapy for the treatment of ovarian cancer. Cytokine Growth Factor Rev 29:109-15
Johnson, Chase L; Green, Daniel S; Zoon, Kathryn C (2015) Human monocytes in the presence of interferons alpha2a and gamma are potent killers of serous ovarian cancer cell lines in combination with paclitaxel and carboplatin. J Interferon Cytokine Res 35:55-62
Bekisz, Joseph; Sato, Yuki; Johnson, Chase et al. (2013) Immunomodulatory effects of interferons in malignancies. J Interferon Cytokine Res 33:154-61
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Baron, Samuel; Finbloom, Joel; Horowitz, Julie et al. (2011) Near eradication of clinically relevant concentrations of human tumor cells by interferon-activated monocytes in vitro. J Interferon Cytokine Res 31:569-73
Tsuno, Takaya; Mejido, Josef; Zhao, Tongmao et al. (2009) IRF9 is a key factor for eliciting the antiproliferative activity of IFN-alpha. J Immunother 32:803-16