Utility of TK/GCV in the context of highly effective oncolysis mediated by a serotype 3 receptor targeted oncolytic adenovirus

M Raki, T Hakkarainen, G J Bauerschmitz, M Särkioja, R A Desmond, A Kanerva, A Hemminki
Gene Therapy 2007, 14 (19): 1380-8
Arming oncolytic adenoviruses with therapeutic transgenes and enhancing transduction of tumor cells are useful strategies for eradication of advanced tumor masses. Herpes simplex virus thymidine kinase (TK) together with ganciclovir (GCV) has been promising when coupled with viruses featuring low oncolytic potential, but their utility is unknown in the context of highly effective infectivity-enhanced viruses. We constructed Ad5/3-Delta24-TK-GFP, a serotype 3 receptor-targeted, Rb/p16 pathway-selective oncolytic adenovirus, where a fusion gene encoding TK and green fluorescent protein (GFP) was inserted into 6.7K/gp19K-deleted E3 region. Ad5/3-Delta24-TK-GFP killed ovarian cancer cells effectively, which correlated with GFP expression. Delivery of GCV immediately after infection abrogated viral replication, which might have utility as a safety switch. Due to the bystander effect, killing of some cell lines in vitro was enhanced by GCV regardless of timing. In murine models of metastatic ovarian cancer, Ad5/3-Delta24-TK-GFP improved antitumor efficacy over the respective replication-deficient virus with GCV. However, GCV did not further enhance efficacy of Ad5/3-Delta24-TK-GFP in vivo. Simultaneous detection of tumor load and virus replication with bioluminescence and fluorescence imaging provided insight into the in vivo kinetics of oncolysis. In summary, TK/GCV may not add antitumor activity in the context of highly potent oncolysis.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"