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Updated: Aug 29, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy
Zi Lai Zhang1, Wei Guo Zou, Chun Xia Luo
1Laboratory of Biotechnology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Abstract:
ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone. In this paper, we put forward a novel concept of Gene-ViroTherapy strategy and in this way, we constructed an armed therapeutic oncolytic adenovirus system, ZD55-gene, which is not only deleted of E1B 55-kD gene similar to ONYX-015, but also armed with foreign antitumor gene. ZD55-gene exhibited similar cytopathic effects and replication kinetics to that of ONYX-015 in vitro. Importantly, the carried gene is expressed and the expression level can increase with the replication of virus. Consequently, a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer. Our data demonstrated that ZD55-gene, which utilizing the Gene-ViroTherapy strategy, is more efficacious than each individual component in vivo.
Insights
A novel Gene-ViroTherapy strategy created an armed oncolytic adenovirus, ZD55-gene. This enhanced adenovirus demonstrated superior anti-tumor efficacy compared to individual components in preclinical cancer models.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Cancer research
Background:
- ONYX-015, an oncolytic adenovirus, shows safety but limited efficacy as a standalone cancer therapy.
- Selective tumor cell replication and killing are key features of therapeutic adenoviruses.
- Enhancing oncolytic viruses with therapeutic genes offers a promising strategy to improve efficacy.
Purpose of the Study:
- To introduce a novel Gene-ViroTherapy strategy for constructing armed oncolytic adenoviruses.
- To evaluate the efficacy of a newly constructed armed adenovirus system, ZD55-gene.
- To compare the in vivo anti-tumor efficacy of ZD55-gene with its individual components.
Main Methods:
- Construction of ZD55-gene, an oncolytic adenovirus deleted of E1B 55-kD gene and armed with a foreign antitumor gene.
- In vitro assessment of ZD55-gene's cytopathic effects and replication kinetics compared to ONYX-015.
- In vivo evaluation of ZD55-CD/5-FU (an example of ZD55-gene) in nude mice bearing human colon cancer xenografts.
Main Results:
- ZD55-gene demonstrated comparable in vitro cytopathic effects and replication kinetics to ONYX-015.
- The carried antitumor gene was expressed, with expression levels increasing with viral replication.
- ZD55-CD/5-FU exhibited significant anti-tumor efficacy in vivo, outperforming individual components.
Conclusions:
- The Gene-ViroTherapy strategy successfully created an armed oncolytic adenovirus system (ZD55-gene).
- ZD55-gene offers enhanced therapeutic potential through combined oncolysis and transgene-mediated anti-tumor effects.
- This armed adenovirus strategy presents a more efficacious approach to cancer treatment than conventional methods.
