OncoTherad® (MRB-CFI-1) nano-immunotherapy reduced tumoral progression in non-muscle invasive bladder cancer through activation of Toll-like signaling pathway

The new modalities for treating patients with high-grade non-muscle invasive bladder cancer (HGNMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. Since NMIBC is sensitive to immunotherapy, Toll-like receptors (TLRs) agonist compounds may represent a potential antitumor therapeutic approach. Our research group developed a synthetic compound, with antitumor and immunological properties, called OncoTherad (R) (MRB-CFI-1). To evaluate the effects of OncoTherad (R) (MRB-CFI-1) and its compounds (P14-16 and CFI-1), thirty-six female C57Bl/6 J mice were divided into six groups (n = 6): Control, Cancer, Cancer + BCG (40 mg), Cancer + OncoTherad (R) (20 mg/mL), Cancer + P14-16 (20 mg/mL) and Cancer + CFI-1 (20 mg/mL). NMIBC was chemically induced (N-ethyl-N-nitrosourea 50 mg/mL) and the treatments were followed for six weeks. The bladder was collected and routinely processed for immunohistochemical analyses of the Toll-Like receptors signaling pathway (TLR2, TLR4, MyD88, IRF-3, IKK-alpha, NF-kappa B, TNF-alpha, TRIF, IFN-gamma, IL-6). The results obtained showed that the tumor progression was 100 % reduced on OncoTherad (R) (MRB-CFI-1) treated animals. Immunohistochemical analysis demonstrated that while the conventional BCG treatment stimulated the canonic pathway, OncoTherad (R) (MRB-CFI-1) stimulated the non-canonical pathway (increasing expression of TLR4, TRIF, IRF, and IFN gamma). OncoTherad (R) (MRB-CFI-1) could be considered a promising therapy in the treatment of NMIBC.