Intravesical interferon-α2b gene therapy with nadofaragene firadenovec-vncg: a contemporary review

Intravesical bacillus Calmette-Guerin (BCG) represents the standard of care therapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC); however, the rate of BCG-unresponsive disease remains high. Cystectomy is the most definitive treatment for patients with this disease entity but is associated with significant morbidity and quality-of-life implications. Recently, several single-arm clinical trials have been conducted to develop alternative treatment options for patients who are ineligible for or decline cystectomy based on guidance from the US Food and Drug Administration (FDA). As a result, several therapeutic options have now emerged, including nadofaragene firadenovec-vncg, an intravesical gene therapy that induces interferon (IFN)-α2b gene expression with resultant direct and indirect anti-tumor effects within the bladder. Today, nadofaragene firadenovec-vncg represents the first-line treatment option for patients with BCG-unresponsive disease as an alternative to cystectomy. Advances in our knowledge of the tumor microenvironment, gene therapy techniques, and tumor biology have contributed to this important discovery, with future studies aimed to optimize the efficacy of this therapy through improved patient selection, disease prognostication, and development of combination strategies.