Bacillus Calmette-Guérin (BCG)-based intravesical immunotherapy has been applied as gold standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) for almost half a century. However, several patients with high-risk disease experience relapse, including those whose condition has worsened and who failed to respond to BCG. Non-significant therapeutic options have been developed for these at-risk patients, for many years. Immunotherapies have shown promising outcomes for bladder cancer treatment. Accordingly, our research group developed the OncoTherad® (MRB-CFI-1) immunotherapy, which has shown positive outcomes in NMIBC treatment. The aim of the current study is to describe, in details, the physicochemical features and potential action mechanisms of OncoTherad® nano-immunotherapy, based on toll-like receptor 4 (TLR4)-mediated interferon and on RANK/RANKL signaling pathways, in animal model with NMIBC. Based on the current findings, OncoTherad® nano-immunotherapy did not have genotoxic effect on the investigated model and did not show signs of limiting local and/or systemic toxicity at therapeutic doses. OncoTherad® nano-immunotherapy was more effective than the BCG treatment, since it reduced by 70% the malignancy rate. Furthermore, it was possible identifying an important action mechanism of OncoTherad®, which was based on the modulation of TLR4-mediated interferon and RANK/RANKL signaling pathways that, altogether, were essential to reduce malignancy rate. OncoTherad® mechanisms in these pathways helped preventing tumor recurrence.
Tissue & cell. 2022 Dec 05 [Epub ahead of print]
W J Fávaro, J C C Alonso, B R de Souza, I B Reis, J M Gonçalves, A C Deckmann, G Oliveira, Q C Dias, N Durán
Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. Electronic address: ., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Paulínia Municipal Hospital, Paulínia, São Paulo, Brazil., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil; Nanomedicine Research Unit (Nanomed), Federal University of ABC (UFABC), Santo André, São Paulo, Brazil. Electronic address: .