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Updated: Mar 25, 2026
Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Evaluation of polymer shielding for adenovirus serotype 6 (Ad6) for systemic virotherapy against human prostate
Tien V Nguyen1, Greg J Heller2, Mary E Barry1
1Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Rochester, Minnesota, USA.
Abstract:
Oncolytic viruses hold promise as "self-amplifying" cancer therapies wherein a virally killed cell can produce thousands of new viral "drugs" that can kill more cancer cells. Adenoviruses (Ads) are one family of oncolytic viruses. Most human studies have used human Ad serotype 5 (Ad5). Unfortunately, most patients are already immune to Ad5 increasing the likelihood that the agent will be neutralized if used as a cancer therapy. In this work, lower seroprevalence Ad6 was tested as a systemic therapy for prostate cancer. Ad5 and Ad6 were injected intravenously a single time in nude mice bearing human prostate tumors, and toxicity and efficacy were assessed. Ad6 was chemically shielded with polyethylene glycol (PEG) to test if this would further improve its pharmacology. Ad6 produced 30-fold lower liver damage and less toxicity than Ad5. Ad6 significantly repressed the growth of androgen-resistant human DU145 prostate tumors and androgen-sensitive LNCaP tumors after single intravenous injection. PEGylation did not change virus distribution, but blunted liver damage and cytokine production by Ad6. PEGylated Ad6 eradicated LNCaP tumors and maintained body mass, but lost potency against the more challenging DU145 tumors. These and other data suggest that low seroprevalent Ad6 has better efficacy and safety than the benchmark oncolytic virus Ad5 for systemic therapy of prostate cancer. These data also indicate that PEGylation may improve Ad6 safety, but that this shielding may reduce oncolytic efficacy after intravenous treatment.
Insights
Adenovirus 6 (Ad6) shows promise as a safer, more effective oncolytic virus for prostate cancer therapy compared to Ad5. Shielding Ad6 with PEG improved safety but reduced efficacy in some models.
Area of Science:
- Oncolytic virotherapy
- Cancer gene therapy
- Viral immunology
Background:
- Oncolytic viruses are self-amplifying cancer therapeutics.
- Adenovirus serotype 5 (Ad5) is a common oncolytic agent but faces pre-existing immunity challenges.
- Prostate cancer requires novel systemic treatment strategies.
Purpose of the Study:
- To evaluate Adenovirus 6 (Ad6) as a systemic oncolytic virotherapy for prostate cancer.
- To compare the safety and efficacy of Ad6 against Ad5.
- To assess the impact of polyethylene glycol (PEG) shielding on Ad6 pharmacology.
Main Methods:
- Intravenous administration of Ad5 and Ad6 in mice with human prostate tumors.
- Assessment of toxicity, viral distribution, and anti-tumor efficacy.
- Evaluation of PEGylated Ad6 for safety and efficacy.
Main Results:
- Ad6 demonstrated significantly lower liver toxicity (30-fold) and overall toxicity compared to Ad5.
- Ad6 repressed growth in both androgen-sensitive and resistant prostate tumors.
- PEGylation reduced Ad6 liver damage and cytokine production but blunted efficacy against resistant tumors.
Conclusions:
- Low seroprevalence Ad6 offers improved safety and efficacy over Ad5 for systemic prostate cancer treatment.
- PEGylation of Ad6 enhances safety but may compromise oncolytic potency.
- Ad6 represents a promising alternative oncolytic virus for prostate cancer therapy.
