Related Experiment Video
Updated: Apr 11, 2026
Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter
Katsuyuki Hamada1, Toshiro Shirakawa2, Shuji Terao3
1Department of Obstetrics and Gynecology, School of Medicine, Ehime University , Shitsukawa, Toon, Ehime Japan.
Abstract:
The use of carrier cells infected with oncolytic viruses in cancer gene therapy is an attractive method because it can overcome viral immunogenicity and induce tumor immunity and significant antitumor activity. To enable human clinical trials of this treatment, acute and chronic toxicity tests must first be performed to ensure safety. IAI.3B promoter, oncolytic adenovirus AdE3-IAI.3B introduced by IAI.3B promoter, and A549 carrier cells infected with AdE3-IAI.3B were highly active in cancer cells but not in normal cells. Freeze-thawing increased the antitumor effect of A549 carrier cells by promoting the translocation of oncolytic adenovirus particles from the nucleus to the cytoplasm following the rupture of the nuclear membranes. No deaths or abnormal blood test data resulted from acute toxicity tests conducted in nude mice after a single dose. In chronic toxicity tests in rabbits, there were no serious side effects after eight doses of 1.25 × 10(7) cells/kg or less for 4 weeks; a significant immune response is known to elicit increased numbers of antiadenovirus antibodies and enlarge the spleen. From these results, it could be concluded that cancer gene therapy of recurrent solid tumors using carrier cells can be safely trialed in humans.
Insights
Carrier cells infected with oncolytic adenovirus show promise for cancer gene therapy. Toxicity tests in animals indicate this approach is safe for human clinical trials of recurrent solid tumors.
Area of Science:
- Oncolytic virotherapy
- Cancer gene therapy
- Immunotherapy
Background:
- Carrier cells infected with oncolytic viruses offer a promising strategy to overcome viral immunogenicity in cancer gene therapy.
- This method aims to induce tumor immunity and significant antitumor activity, necessitating safety evaluations for clinical application.
Purpose of the Study:
- To evaluate the safety and efficacy of carrier cells infected with oncolytic adenovirus (AdE3-IAI.3B) for cancer gene therapy.
- To assess acute and chronic toxicity in animal models to support human clinical trials.
Main Methods:
- Oncolytic adenovirus AdE3-IAI.3B, utilizing the IAI.3B promoter, was introduced into A549 carrier cells.
- Cytotoxicity was assessed in cancer and normal cells. Freeze-thawing effects on carrier cells were investigated.
- Acute toxicity was evaluated in nude mice after a single dose.
- Chronic toxicity was assessed in rabbits over 4 weeks with repeated doses.
Main Results:
- AdE3-IAI.3B demonstrated high activity against cancer cells with minimal impact on normal cells.
- Freeze-thawing enhanced the antitumor effect by facilitating oncolytic adenovirus translocation within carrier cells.
- Acute toxicity tests showed no deaths or abnormal blood parameters in mice.
- Chronic toxicity tests in rabbits revealed no severe side effects at doses up to 1.25 × 10^7 cells/kg, though increased antiadenovirus antibodies and spleen enlargement were observed, indicating an immune response.
Conclusions:
- Cancer gene therapy using carrier cells infected with oncolytic adenovirus AdE3-IAI.3B is highly active against cancer cells and shows a favorable safety profile.
- The observed toxicity profile supports the initiation of human clinical trials for recurrent solid tumors.
