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2009: Hakkarainen Tanja; Rajecki Maria; Sarparanta Mirkka; Tenhunen Mikko; Airaksinen Anu J; Desmond Renée A; Kairemo Kalevi; Hemminki Akseli
Targeted radiotherapy for prostate cancer with an oncolytic adenovirus coding for human sodium iodide symporter.
Clinical cancer research : an official journal of the American Association for Cancer Research 2009;15(17):5396-403.
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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