TY - JOUR
T1 - Interferon gene therapy with nadofaragene firadenovec for bladder cancer
T2 - from bench to approval
AU - Martini, Alberto
AU - Tholomier, Côme
AU - Mokkapati, Sharada
AU - Dinney, Colin P.N.
N1 - Funding Information:
AM owns shares of Oltre Medical Consulting, LLC, Toulouse, FRrance. CD receives Cancer Center Support Grant funding from the National Institutes for Health/National Cancer Institute award number P30CA016672 at MD Anderson Cancer Center, has received grants and personal fees from FKD Therapies, and is a creator of intellectual property owned by UT/MDACC related to the use of genetic alterations as a predictive biomarker for response to nadofaragene firadenovec.
Publisher Copyright:
Copyright © 2023 Martini, Tholomier, Mokkapati and Dinney.
PY - 2023
Y1 - 2023
N2 - Bladder cancer is a prevalent malignancy with limited therapeutic options, particularly for patients who are unresponsive to Bacillus Calmette-Guérin (BCG). The approval of interferon-α (IFNα) gene therapy with nadofaragene firadenovec (Adstiladrin®), the first gene therapy for genitourinary malignancies, has provided a promising alternative. This article reviews the research and milestones that led to the development and approval of nadofaragene firadenovec. Bladder cancer is well-suited for gene therapy due to direct access to the bladder and the availability of urine and tissue samples for monitoring. Early challenges included effective gene transfer across the urothelium, which was overcome initially by modulating the expression of coxsackie/adenovirus receptor (CAR) and, ultimately, by disrupting the urothelial barrier with Syn3. Nadofaragene firadenovec is a modified adenoviral vector carrying the IFNα gene. Clinical trials have shown promising results, with high response rates and manageable adverse events. Ongoing research focuses on improving patient selection, identifying biomarkers for response prediction, exploring alternative vectors for enhanced transfection efficiency, and developing combination strategies targeting resistance mechanisms. The approval of nadofaragene firadenovec marks a significant milestone in the field of gene therapy for bladder cancer, and future developments hold promise for further enhancing its efficacy and impact.
AB - Bladder cancer is a prevalent malignancy with limited therapeutic options, particularly for patients who are unresponsive to Bacillus Calmette-Guérin (BCG). The approval of interferon-α (IFNα) gene therapy with nadofaragene firadenovec (Adstiladrin®), the first gene therapy for genitourinary malignancies, has provided a promising alternative. This article reviews the research and milestones that led to the development and approval of nadofaragene firadenovec. Bladder cancer is well-suited for gene therapy due to direct access to the bladder and the availability of urine and tissue samples for monitoring. Early challenges included effective gene transfer across the urothelium, which was overcome initially by modulating the expression of coxsackie/adenovirus receptor (CAR) and, ultimately, by disrupting the urothelial barrier with Syn3. Nadofaragene firadenovec is a modified adenoviral vector carrying the IFNα gene. Clinical trials have shown promising results, with high response rates and manageable adverse events. Ongoing research focuses on improving patient selection, identifying biomarkers for response prediction, exploring alternative vectors for enhanced transfection efficiency, and developing combination strategies targeting resistance mechanisms. The approval of nadofaragene firadenovec marks a significant milestone in the field of gene therapy for bladder cancer, and future developments hold promise for further enhancing its efficacy and impact.
KW - BCG unresponsive bladder cancer
KW - bladder cancer
KW - gene therapy
KW - immunogene therapy
KW - novel medications
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U2 - 10.3389/fimmu.2023.1260498
DO - 10.3389/fimmu.2023.1260498
M3 - Short survey
C2 - 37705979
AN - SCOPUS:85170557484
SN - 1664-3224
VL - 14
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1260498
ER -