4.6 Article

New synthetic nano-immunotherapy (OncoTherad?) for non-muscle invasive bladder cancer: Its synthesis, characterization and anticancer property

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TISSUE & CELL
卷 80, 期 -, 页码 -

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CHURCHILL LIVINGSTONE
DOI: 10.1016/j.tice.2022.101988

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Non-muscle invasive bladder cancer; OncoTherad ?; Toll-like receptors; Nanotechnology; Immunotherapy; Nanomedicine

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BCG-based intravesical immunotherapy is the gold standard treatment for high-risk non-muscle invasive bladder cancer. However, some high-risk patients experience relapse and do not respond to BCG. Our research group developed OncoTherad (R) nano-immunotherapy, which showed positive outcomes and mechanisms of action in an animal model with NMIBC. OncoTherad (R) nano-immunotherapy was more effective than BCG treatment, reducing the malignancy rate by 70% through modulation of TLR4-mediated interferon and RANK/RANKL signaling pathways.
Bacillus Calmette-Gue & PRIME;rin (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 (R) (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 (R) 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 (R) 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 (R) nanoimmunotherapy 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 (R), which was based on the modulation of TLR4-mediated interferon and RANK/RANKL signaling pathways that, altogether, were essential to reduce malignancy rate. OncoTherad (R) mechanisms in these pathways helped preventing tumor recurrence.

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