Targeted radiotherapy for prostate cancer with an oncolytic adenovirus coding for human sodium iodide symporter.

Academic Article

Abstract

  • PURPOSE: Oncolytic adenoviruses are promising tools for cancer therapy. Although several clinical reports have indicated both safety and promising antitumor capabilities for these viruses, there are only a few examples of complete tumor eradication. Thus, the antitumor efficacy of oncolytic adenoviruses needs to be improved. One potentially useful approach is combination with radiotherapy. EXPERIMENTAL DESIGN: To target systemically administered radioiodide to tumors, we created Ad5/3-Delta24-human sodium iodide symporter (hNIS), a Rb-p16 pathway selective infectivity enhanced oncolytic adenovirus encoding hNIS. RESULTS: Ad5/3-Delta24-hNIS replication effectively killed prostate cancer cells in vitro and in vivo. Also, the virus-mediated radioiodide uptake into prostate cancer cells in vitro and into tumors in vivo. Furthermore, Ad5/3-Delta24-hNIS with radioiodide was significantly more effective than virus alone in mice with prostate cancer xenografts. CONCLUSIONS: These results suggest that oncolytic adenovirus-mediated targeted radiotherapy might be a potentially useful option for enhancing the efficacy or adenoviral virotherapy.
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    Keywords

  • Adenocarcinoma, Adenoviridae, Animals, Cell Line, Tumor, Combined Modality Therapy, Genetic Therapy, Humans, Iodine Isotopes, Lung Neoplasms, Male, Mice, Oncolytic Virotherapy, Oncolytic Viruses, Prostatic Neoplasms, Symporters, Xenograft Model Antitumor Assays
  • Digital Object Identifier (doi)

    Author List

  • Hakkarainen T; Rajecki M; Sarparanta M; Tenhunen M; Airaksinen AJ; Desmond RA; Kairemo K; Hemminki A
  • Start Page

  • 5396
  • End Page

  • 5403
  • Volume

  • 15
  • Issue

  • 17