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http://dx.doi.org/10.21037/tau.2017.09.20DOI Listing

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Background: The intravesical gene therapy nadofaragene firadenovec (rAd-IFNα/Syn3) was FDA approved in 2022 for non-muscle invasive bladder cancer (NMIBC) unresponsive to frontline treatment with BCG, and the first gene therapy developed for bladder cancer. This non-replicating recombinant adenovirus vector delivers a copy of the human interferon alpha-2b gene into urothelial and tumor cells, causing them to express this pleotropic cytokine with potent antitumor effects.

Objective: To provide a historical overview describing how several decades of preclinical and clinical studies investigating the role of interferon in the treatment of bladder cancer ultimately led to the development of gene therapy with nadofaragene for NMIBC.

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Article Synopsis
  • High-risk non-muscle invasive bladder cancer patients in Latin America have experienced BCG shortages, prompting studies on the effectiveness of reduced-dose (RD) versus full-dose (FD) BCG treatments.
  • A retrospective study on 200 patients revealed that those receiving FD BCG had significantly lower recurrence rates and progression to muscle-invasive bladder cancer compared to those on RD BCG.
  • Although RD treatment had fewer treatment discontinuations due to toxicity, it was linked to poorer oncological outcomes, suggesting that full-dose BCG is more effective for high-risk patients.
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