A1 Refereed original research article in a scientific journal
Targeted Radiotherapy for Prostate Cancer with an Oncolytic Adenovirus Coding for Human Sodium Iodide Symporter
Authors: Hakkarainen T, Rajecki M, Sarparanta M, Tenhunen M, Airaksinen AJ, Desmond RA, Kairemo K, Hemminki A
Publisher: AMER ASSOC CANCER RESEARCH
Publication year: 2009
Journal: Clinical Cancer Research
Journal name in source: CLINICAL CANCER RESEARCH
Journal acronym: CLIN CANCER RES
Volume: 15
Issue: 17
First page : 5396
Last page: 5403
Number of pages: 8
ISSN: 1078-0432
DOI: https://doi.org/10.1158/1078-0432.CCR-08-2571
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-Delta 24-human sodium iodide symporter (hNIS), a Rb-p16 pathway selective infectivity enhanced oncolytic adenovirus encoding hNIS.Results: Ad5/3-Delta 24-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-Delta 24-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. (Clin Cancer Res 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-Delta 24-human sodium iodide symporter (hNIS), a Rb-p16 pathway selective infectivity enhanced oncolytic adenovirus encoding hNIS.Results: Ad5/3-Delta 24-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-Delta 24-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. (Clin Cancer Res 2009;15(17):5396-403)
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