Open AccessConditionally replicating adenovirus improves gene replication efficiency and anticancer effect of E1‐deleted adenovirus carrying TRAIL in head and neck squamous cell carcinoma
Author(s) -
Shim SeonHui,
Lee ChoonTaek,
Hun Hah J.,
Lee JaeJung,
Park SeokWoo,
Heo Dae Seog,
Sung MyungWhun
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01409.x
Subject(s) - oncolytic virus , genetic enhancement , oncolytic adenovirus , cancer research , adenoviridae , cell culture , viral vector , biology , head and neck squamous cell carcinoma , virology , luciferase , cancer , gene , virus , head and neck cancer , transfection , genetics , recombinant dna
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‐TRAIL alone did not. In conclusion, this combined strategy using CRAd and adenovirus carrying a therapeutic gene increased the gene transfer rate and enhanced antitumor effects. We expect that this combination strategy could be extended to a multitarget cancer gene therapy by combining multiple adenoviruses and CRAd. ( Cancer Sci 2009)