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

Clin Cancer Res. 2009 Sep 1;15(17):5396-403. doi: 10.1158/1078-0432.CCR-08-2571. Epub 2009 Aug 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / therapy*
  • Adenoviridae / genetics
  • Animals
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Genetic Therapy
  • Humans
  • Iodine Isotopes / pharmacology
  • Iodine Isotopes / therapeutic use
  • Lung Neoplasms / radiotherapy
  • Lung Neoplasms / therapy*
  • Male
  • Mice
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / therapy*
  • Symporters / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Iodine Isotopes
  • Symporters
  • sodium-iodide symporter