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


METHODS
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.
Hakkarainen
Tanja
T
Cancer Gene Therapy Group, Molecular Cancer Biology Program & Transplantation Laboratory & Haartman Institute & Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Rajecki
Maria
M
Sarparanta
Mirkka
M
Tenhunen
Mikko
M
Airaksinen
Anu J
AJ
Desmond
Renée A
RA
Kairemo
Kalevi
K
Hemminki
Akseli
A
D000230:Adenocarcinoma / Q000532:radiotherapy / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D015316:Genetic Therapy; D006801:Humans; D007456:Iodine Isotopes / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics; D011471:Prostatic Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D027981:Symporters / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D007456:Iodine Isotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters