Association of immunotherapy with OncoTherad® (MRB-CFI-1) and platelet rich plasma in the treatment of Chemically Induced Ovarian Cancer in rats: evaluation of immunological checkpoints and RANK/RANKL pathway

Abstract

Among gynecological tumors, ovarian cancer (OC) is the most lethal, responsible for the highest mortality among cancers of the female reproductive system and the fifth neoplasm that causes more deaths in women. The chemotherapy drugs used as platinum / paclitaxel have several toxic effects in addition to acquired resistance to the drug during treatment. Considering the importance of development of drugs that act as modulators of the immune system, our research group developed a nanostructured synthetic compound called Onco Therad® (MRB-CFI-1) with antitumor and immunological properties reported in in bladder cancer of animals and humans, involving the signaling pathway for interferon mediated by Toll-like receptors (TLRs) 2 and 4. The tumor microenvironment of OC involves an immunosuppressive network of leukocytes and mediators, as well as the co-optation of immunological checking pathways favors the establishment of the tumor and the evasion of the host's immune system. Given the importance of the modulation of the immune system receptors by phosphate species and their relationships with activated platelets, our research group investigated the importance of Platelet Rich Plasma (PRP) in modulating these receptors and found that PRP exerts antitumor effects mediated by imune system. PRP still has cytoprotective effects and improves ovarian function in humans. Thus, the objective of the project is to evaluate the effects of immunotherapy with Onco Therad® and the administration of PRP, 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 imune checkpoints PD-1 / PDL-1 and CTLA-4 and the RANK / RANKL / OPG signaling pathway will be investigated, in addition to the evaluation of platelet growth factors IGF-1 and TGF-². The association of Onco Therad® and PRP can support the development of a new drug and thus another therapeutic alternative for OC. (AU)