Abstract

This study reports the effects of a promising therapeutic option for non-muscle invasive bladder cancer (NMIBC) based on OncoTherad intravesical immunotherapy in an appropriated animal model. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein, which exhibits immunomodulatory and antitumor properties. Biochemical parameters in rats, mice and rabbits treated intravesically with OncoTherad at doses of 20-100 mg/kg, did not differed statistically from their respective controls, exhibiting no systemic toxic effects. All the target organs did not present inflammation and histopathological changes. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea (MNU). Bacillus Calmette-Guérin (BCG) were used as positive control in the animal models. The results demonstrated that animals treated with OncoTherad distinctly showed a significant histopathological recovery from the cancer state of animals (80%) when compared to BCG treatment. In addition, BCG and OncoTherad intravesical immunotherapies were able to restore TLR2 levels. However, OncoTherad increased of TLR4 levels when compared to BCG. Thus, the activation of TLR4 by Oncotherad was efficient in reducing urothelial neoplastic progression. All data are indicative that of OncoTherad is a feasible candidate for the NMIBC treatment.

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