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Association of immunotherapy with OncoTherad® (MRB-CFI-1) and erythropoietin in the treatment of chemically induced ovarian Cancer in rats: assessment of angiogenesis and immunological checkpoints

Grant number: 20/07897-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2021
Effective date (End): January 31, 2022
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal researcher:Wagner José Fávaro
Grantee:Giovana Leme
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

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 more 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 has 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 tumoral microenvironment of CO involves a complex immunosuppressive network of leukocytes and immunosuppressive mediators, as well as the co-optation of immune system checking pathways that favor the establishment of the tumor and the evasion of the host's immune response. 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. Therefore, the possible mechanisms of action of this therapeutic association in the checkpoints of the PD-1 / PDL-1 and CTLA-4 immune system and in the RANK / RANKL / OPG signaling pathway, in addition to the assessment of angiogenic activity using a pro angiogenic (VEGF) and anti angiogenic marker ( Endostatin). The combination of OncoTherad® and EPO can support the development of a new drug and thus another therapeutic alternative for CO.