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The development of interferon-based gene therapy for BCG unresponsive bladder cancer: from bench to bedside

  • Jonathan J. Duplisea
  • Sharada Mokkapati
  • Devin Plote
  • Kimberly S. Schluns
  • David J. McConkey
  • Seppo Yla-Herttuala
  • Nigel R. Parker
  • Colin P. Dinney
Invited Review
  • 43 Downloads

Abstract

Background and Purpose

BCG unresponsive bladder cancer is an inherently resistant disease state for which the preferred treatment is radical cystectomy. To date, no effective intravesical therapies exist for patients who possess these resistant tumors. For this reason, many research groups are actively investigating/testing novel therapeutic agents to aid in bladder preservation for this patient population. This review article describes our 15-year experience developing and testing IFN-based gene therapy.

Methods

A comprehensive review was performed of all studies pertaining to IFN-based gene therapy for non-muscle invasive bladder cancer from 2003 to 2018.

Results and Conclusions

Over the past two decades, gene therapy has evolved into a powerful tool in our fight against cancer. After overcoming the initial barriers associated with gene delivery to the bladder, we have made significant strides forward in developing this novel therapeutic strategy for the treatment of this inherently resistant disease state. Our results to date are very encouraging; however, much work lies ahead to better understand and optimize this novel approach for treating non-muscle invasive bladder.

Keywords

BCG unresponsive bladder cancer Gene therapy Interferon-α Instiladrin 

Notes

Author contributions

JD literature review and manuscript writing. SM manuscript editing/data collection. DP manuscript editing/data collection. KS manuscript editing. SYH manuscript writing/editing. NP manuscript writing/editing. CD manuscript oversight/writing/editing.

Funding

The University of Texas MD Anderson SPORE in Genitourinary Cancer P50CA091846, NIH/NCI under P30CA016672.

Compliance with ethical standards

Conflict of interest

Nigel Parker: leadership, consulting, and research funding—FKD Therapies Oy. Seppo Yla-Herttulla: consultant for FKD Therapies Oy. Colin Dinney: consultant on advisory board for FKD Therapies Oy. All remaining authors declare no conflicts of interest.

Research involving human participants and/or animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

Informed consent was obtained from all individual participants of clinical studies included in this review article.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jonathan J. Duplisea
    • 1
  • Sharada Mokkapati
    • 1
  • Devin Plote
    • 2
  • Kimberly S. Schluns
    • 3
  • David J. McConkey
    • 4
  • Seppo Yla-Herttuala
    • 5
  • Nigel R. Parker
    • 6
  • Colin P. Dinney
    • 1
  1. 1.Department of UrologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Cancer BiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of ImmunologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.James Buchanan Brady Urological Institute, Johns Hopkins Greenberg Bladder Cancer InstituteJohns Hopkins University, School of MedicineBaltimoreUSA
  5. 5.A.I.Virtanen Institute, University of Eastern Finland and Gene Therapy UnitKuopio University HospitalKuopioFinland
  6. 6.Hamesman Ltd.LondonUK

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