Cretostimogene Grenadenorepvec

Non-muscle-invasive bladder cancer (NMIBC) accounts for roughly 75% of newly diagnosed bladder cancer and associates with high risk of recurrence and progression. Intravesical therapy remains the cornerstone of NMIBC management following transurethral resection of bladder tumor (TURBT). For low-risk NMIBC, immediate single instillation of chemotherapy after TURBT effectively reduces recurrence. Intermediate-risk patients could benefit from either intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) instillation, with emerging therapies such as UGN-102 chemoablation showing promise. For high/very high-risk NMIBC, full-dose, 3-year BCG instillation remains the standard of care, However, global BCG shortages and treatment failures have prompted the need for alternative strategies. Optimization of BCG regimens, such as two induction courses, may preserve efficacy while improving feasibility. Moreover, alternative agents such as sequential gemcitabine and docetaxel instillation have demonstrated favorable outcomes in both BCG-naïve and BCG-unresponsive patients. For those with BCG failure, a number of novel therapies are under active investigation. Gene therapy (nadofaragene firadenovec), oncolytic viral therapy (CG0070), interleukin-15 superagonist (Nogapendekin alfa-inbakicept), and innovative drug delivery systems (TAR-200) have shown encouraging clinical potential in this population. This review provides an overview of current intravesical treatment strategies for NMIBC across different risk groups and highlights promising new approaches aimed at overcoming the limitations of BCG therapy.

Despite major gains with immunotherapy, many tumors remain non-responsive because of poor antigen release and a suppressive tumor microenvironment (TME). Oncolytic virotherapy (OVT) directly lyses cancer cells and secondarily inflames the TME via immunogenic cell death and type I interferon (IFN-I) signaling. Here we present primary clinical and preclinical evidence on (i) mechanisms that govern OV selectivity and immune priming, (ii) genetic engineering strategies linked to clinical signals, and (iii) translational lessons across species, with emphasis on companion-animal oncology as a bridge to human trials. We highlight trials where OVs prime checkpoint response (e.g., DNX-2401→pembrolizumab in recurrent glioblastoma) and where vector design (e.g., TK-deleted vaccinia, CG0070) or payloads (e.g., IFNβ, NIS) drive measurable benefit. We conclude with actionable priorities, patient selection by IFN-pathway competence, receptor-tropism panels, and rational OV-ICI sequencing, to accelerate durable responses.