Conditionally replicating adenovirus improves gene replication efficiency and anticancer effect of E1-deleted adenovirus carrying TRAIL in head and neck squamous cell carcinoma

Cancer Science
Seon-Hui ShimMyung-Whun Sung

Abstract

To overcome the low efficiency of gene therapy, we combined a conditionally replicating adenovirus (CRAd) and an adenoviral vector with a therapeutic gene. CRAd has an oncolytic activity in cancer cells with abnormal Rb activity and helps the replication of therapeutic genes incorporated in the E1-deleted adenovirus. We investigated the anticancer effect of a combination of CRAd and adenovirus carrying tumor necrosis factor-related apoptosis inducing ligand (ad-TRAIL). We expected to see increased gene expression in cancer cells as well as an antitumor effect. With the combined application of CRAd and ad-luciferase in head and neck cancer cell lines, we observed considerably increased luciferase activity that was 10- to 50-fold greater than with ad-luciferase alone. The combination of CRAd and ad-TRAIL showed significant suppression of growth in cell lines and increased the sub-G(1) portion of cells 30-fold compared to any single treatment. The expression of TRAIL was highly amplified by the combined treatment and was accompanied by expression of molecules related to apoptosis. In a xenograft animal model, mice treated with CRAd and ad-TRAIL showed complete regression of established tumors, whereas mice treated with CRAd or ad-...Continue Reading

References

Oct 31, 1998·Current Opinion in Immunology·T S Griffith, D H Lynch
Jul 2, 2003·Cancer Gene Therapy·Ja Young SeolChoon-Taek Lee
Jul 15, 2003·Gene Therapy·T-G HuangS L C Woo
Dec 5, 2003·International Journal of Molecular Medicine·Seung Hun JangChoon-Taek Lee
Feb 24, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qian HuangChuan-Yuan Li
Nov 20, 2004·Cancer Gene Therapy·Lidong Zhang, Bingliang Fang

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Citations

Jul 14, 2012·Expert Opinion on Biological Therapy·Donavon C Hiss, Burtram C Fielding
Apr 22, 2011·International Journal of Cancer. Journal International Du Cancer·Guan JiangYan-Qun Liu
Jan 8, 2015·Annals of Surgical Oncology·Soon-Hyun AhnJin Ho Paik

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