Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice.

Abstract

BACKGROUND:

Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads.

METHODS:

Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies.

RESULTS:

Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment.

CONCLUSION:

Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor.

• Authors: Pei-Hsin Cheng, Xiao-Mei Rao, Stephen L Wechman, Xiao-Feng Li, Kelly M McMasters, Heshan Sam Zhou
• Journal: BMC cancer (BMC Cancer) Vol. 15 Pg. 716 (Oct 16 2015) ISSN: 1471-2407 [Electronic] England
• PMID: 26475304 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin E

Topics

• Adenocarcinoma (genetics, therapy)
• Adenoviridae (genetics)
• Animals
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cyclin E (biosynthesis, genetics)
• Disease Models, Animal
• Gene Expression Regulation, Neoplastic
• Humans
• Isografts
• Lung Neoplasms (genetics, therapy)
• Mice
• Oncolytic Virotherapy
• Oncolytic Viruses
• Xenograft Model Antitumor Assays