The Oncolytic Adenovirus XVir-N-31 as a Novel Therapy in Muscle-Invasive Bladder Cancer

Hum Gene Ther. 2019 Jan;30(1):44-56. doi: 10.1089/hum.2018.026. Epub 2018 Aug 3.

Abstract

Muscle-invasive bladder cancer represents approximately 25% of diagnosed bladder cancer cases and carries a significant risk of death. Oncolytic viruses are novel antitumor agents with the ability to selectively replicate and lyse tumor cells while sparing healthy tissue. We explored the efficiency of the oncolytic YB-1-selective adenovirus XVir-N-31 in vitro and in an orthotopic mouse model for bladder cancer by intramural injection under ultrasound guidance. We demonstrated that XVir-N-31 replicated in bladder cancer cells and induced a stronger immunogenic cell death than wild-type adenovirus by facilitating enhanced release of HMGB1 and exosomal Hsp70. The intratumoral delivery of XVir-N-31 by ultrasound guidance delayed tumor growth in an immunodeficient model, demonstrating the feasibility of this approach to deliver oncolytic viruses directly into the tumor.

Keywords: MIBC; YB-1; adenovirus; bladder cancer; oncolytic; ultrasound guided; virotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cell Death / genetics
  • Cell Line, Tumor
  • Disease Models, Animal
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Therapy* / methods
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Humans
  • Mice
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses / genetics*
  • Transgenes
  • Tumor Burden
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*
  • Xenograft Model Antitumor Assays
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism

Substances

  • Y-Box-Binding Protein 1
  • YBX1 protein, human