Association of immunotherapy with OncoTherad® (MRB-CFI-1) and erythropoietin in the treatment of Chemically induced Ovarian Cancer in rats: evaluation of the cytotoxic inflammatory response

Abstract

Among gynecological tumors, ovarian cancer (OC) is the most lethal and the most difficult to be diagnosed, being responsible for the highest mortality among cancers of the female reproductive system and the fifth type of cancer that causes most deaths among women. Conventional chemotherapy drugs such as platinum / paclitaxel have numerous toxic effects in addition to resistance to the drug acquired during treatment. Considering the importance of developing drugs that act as modulators of the immune system, our research group developed a nanostructured synthetic compound called OncoTherad® (MRB-CFI-1) with anti-tumor and immunological properties reported in bladder cancer in animals and humans, mainly involving the signaling pathway for interferon mediated by Toll-like receptors (TLRs) 2 and 4. Erythropoietin (EPO) can exert several non-hematopoietic functions such as immunomodulation, anti-inflammatory or antioxidant and cytoprotective actions including in the female reproductive system. The tumor microenvironment of OC involves a complex immunosuppressive network of leukocytes and immunosuppressive mediators that favor the establishment of the tumor and its evasion from the immune system. Thus, the objective of the project is to evaluate the effects of immunotherapy with OncoTherad® and the administration of EPO, alone or in combination, in the treatment of chemically induced ovarian cancer in Fischer 344 rats. For this purpose, the possible mechanisms of action of this therapeutic association in the signaling pathway of Toll-like receptors (TLRs 2 and 4) will be investigated in addition to the evaluation of the inflammatory response profile involving the activation of macrophages using markers of antitumor cytotoxic activity (IFN-³, iNOS and total macrophages F4 / 80 + ) or pro tumor (IL-6, M2 CD163 + macrophages and Foxp3 + regulatory T lymphocytes). The combination of OncoTherad® and EPO can support the development of a new drug and thus another therapeutic alternative for OC. (AU)