Journal article
Bacillus Calmette‐Guérin (BCG) and Interferon (IFN) Gene Therapy for Combination Bladder Cancer Treatment: A Mathematical Model for Improved Efficacy and Tolerability
Advanced theory and simulations, Vol.9(2), e01147
02/2026
DOI: 10.1002/adts.202501147
Abstract
Intravesical instillation of Bacillus Calmette‐Guérin (BCG) bacteria represents the gold standard adjuvant therapy for non‐muscle‐invasive bladder cancer following tumor resection. Despite treatment efficacy, ≈50% of patients exhibit resistance to treatment or cannot complete the therapeutic course due to severe side effects. Nadofaragene firadenovec (IFN‐gene) therapy, recently FDA‐approved for BCG‐unresponsive patients, offers potential benefits by utilizing intravesical adenoviral infection to produce high local IFNα levels sustained for several days. By simulating changes in treatment protocols, mathematically, how combining these agents may provide more effective and better‐tolerated regimens for BCG non‐responder or intolerant patients is explored. Four equations are employed to model the dynamics of tumor cells, immune system responses, and BCG with IFN‐gene therapy interactions. The model predicts that improved outcomes, compared to basic protocols, can be achieved. Specifically, combining BCG and IFN‐gene therapy reduces the non‐responder rate from 52% to 32%. Moreover, reducing BCG dosage while combining it with IFN‐gene therapy in prolonged maintenance courses with five additional treatment cycles reduces non‐responders to 10%. IFN‐gene therapy creates stable windows of opportunity for enhanced immune system responses, achieving improved BCG‐stimulated malignant urothelial cell killing. The protocol assists future rational clinical trial planning to test these hypotheses.
Details
- Title: Subtitle
- Bacillus Calmette‐Guérin (BCG) and Interferon (IFN) Gene Therapy for Combination Bladder Cancer Treatment: A Mathematical Model for Improved Efficacy and Tolerability
- Creators
- Svetlana Bunimovich-Mendrazitsky - Ariel UniversityMichael A. O'Donnell - University of IowaSarel Halachmi - Bnai Zion Medical CenterNatalie Kronik - Tel Aviv Sourasky Medical Center
- Resource Type
- Journal article
- Publication Details
- Advanced theory and simulations, Vol.9(2), e01147
- DOI
- 10.1002/adts.202501147
- ISSN
- 2513-0390
- eISSN
- 2513-0390
- Publisher
- Wiley
- Language
- English
- Electronic publication date
- 10/25/2025
- Date published
- 02/2026
- Academic Unit
- Urology
- Record Identifier
- 9985019026902771
Metrics
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