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Published on: March 5, 2020
Photoactivatable oncolytic adenovirus for optogenetic cancer therapy
Yasuko Hagihara1, Ayaka Sakamoto2, Takashi Tokuda3,4
1Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan.
Abstract:
Virotherapy using oncolytic adenovirus is an effective anticancer strategy. However, the tumor selectivity of oncolytic adenoviruses is not enough high. To develop oncolytic adenovirus with a low risk of off-tumor toxicity, we constructed a photoactivatable oncolytic adenovirus (paOAd). In response to blue light irradiation, the expression of adenoviral E1 genes, which are necessary for adenoviral replication, is induced and replication of this adenovirus occurs. In vitro, efficient lysis of various human cancer cell lines was observed by paOAd infection followed by blue light irradiation. Importantly, there was no off-tumor toxicity unless the cells were irradiated by blue light. In vivo, tumor growth in a subcutaneous tumor model and a mouse model of liver cancer was significantly inhibited by paOAd infection followed by blue light irradiation. In addition, paOAd also showed a therapeutic effect on cancer stem cells. These results suggest that paOAd is useful as a safe and therapeutically effective cancer therapy.
Insights
Photoactivatable oncolytic adenovirus (paOAd) offers a safer cancer therapy. Blue light activates paOAd to target and destroy cancer cells, minimizing off-tumor toxicity for improved virotherapy outcomes.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Oncolytic adenovirus virotherapy is a promising cancer treatment.
- Current oncolytic adenoviruses lack sufficient tumor selectivity, leading to off-tumor toxicity.
- Developing targeted viral therapies is crucial for improving patient safety.
Purpose of the Study:
- To engineer a photoactivatable oncolytic adenovirus (paOAd) for enhanced tumor selectivity.
- To investigate the safety and efficacy of paOAd in preclinical cancer models.
- To assess the therapeutic potential of paOAd against cancer stem cells.
Main Methods:
- Construction of a photoactivatable oncolytic adenovirus (paOAd) activated by blue light.
- In vitro assessment of paOAd-mediated cancer cell lysis upon blue light irradiation.
- In vivo evaluation of paOAd efficacy in subcutaneous and liver cancer mouse models.
- Analysis of paOAd's therapeutic effect on cancer stem cells.
Main Results:
- paOAd efficiently lysed various human cancer cell lines in vitro following blue light exposure.
- No significant off-tumor toxicity was observed without blue light irradiation.
- paOAd treatment with blue light significantly inhibited tumor growth in vivo.
- paOAd demonstrated therapeutic efficacy against cancer stem cells.
Conclusions:
- paOAd represents a novel, photoactivatable oncolytic adenovirus with improved safety and efficacy.
- Blue light-induced activation of paOAd enables targeted cancer therapy with reduced off-tumor effects.
- paOAd shows potential as a safe and effective therapeutic agent for various cancers, including those driven by cancer stem cells.
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