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Published on: March 13, 2018
Targeted radiotherapy for prostate cancer with an oncolytic adenovirus coding for human sodium iodide symporter
Tanja Hakkarainen1, Maria Rajecki, Mirkka Sarparanta
1Cancer Gene Therapy Group, Molecular Cancer Biology Program & Transplantation Laboratory & Haartman Institute & Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
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.
Insights
Oncolytic adenoviruses combined with radioiodide show promise for cancer therapy. This novel approach enhances tumor cell killing and uptake of radioiodide, improving treatment efficacy in preclinical models.
Area of Science:
- Oncolytic virotherapy
- Cancer radiotherapy
- Gene therapy
Background:
- Oncolytic adenoviruses offer potential for cancer treatment, but complete tumor eradication remains a challenge.
- Combination therapy, particularly with radiotherapy, is being explored to enhance antitumor efficacy.
Purpose of the Study:
- To develop and evaluate an oncolytic adenovirus encoding the human sodium iodide symporter (hNIS) for targeted radioiodide delivery.
- To assess the efficacy of this combined oncolytic virotherapy and targeted radiotherapy in preclinical prostate cancer models.
Main Methods:
- Engineered Ad5/3-Delta24-hNIS oncolytic adenovirus encoding hNIS for targeted radioiodide uptake.
- Evaluated virus replication and cancer cell killing in vitro and in vivo.
- Assessed virus-mediated radioiodide uptake in cancer cells and tumors.
- Compared efficacy of Ad5/3-Delta24-hNIS with and without radioiodide in mouse xenograft models.
Main Results:
- Ad5/3-Delta24-hNIS demonstrated effective replication and killing of prostate cancer cells in vitro and in vivo.
- The virus successfully mediated radioiodide uptake into prostate cancer cells and tumors.
- Combination of Ad5/3-Delta24-hNIS with radioiodide showed significantly enhanced efficacy compared to the virus alone in preclinical models.
Conclusions:
- Oncolytic adenovirus-mediated delivery of hNIS enables targeted radiotherapy.
- This combined approach holds potential for improving the efficacy of adenoviral virotherapy against cancer.
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