Immune Netw.  2007 Dec;7(4):179-185. 10.4110/in.2007.7.4.179.

Enhancement of Transduction Efficiency and Antitumor Effects of IL-12N220L-expressing Adenovirus by Co-delivery of DOTAP

• Youn JI
• Jin HT
• Sung YC

• KMID: 2150635
• DOI: http://doi.org/10.4110/in.2007.7.4.179

Abstract

BACKGROUND: Adenovirus (Ad) vectors have been widely used for many gene therapy applications because of their high transduction ability and broad tropism. However, their utility for cancer gene therapy is limited by their poor transduction into cancer cells lacking the primary receptor, coxsackievirus and adenovirus receptor (CAR).
METHODS
To achieve CAR-independent gene transfer via Ad, we pretreated Ad with 1,2-dioleoyl-3- trimethylammonium propane (DOTAP) and analyzed their transduction efficiency into cancer cells in vitro and in vivo comparing with the virus alone.
RESULTS
Treatment of DOTAP significantly increased adenoviral gene transfer in tumor cells in vitro. Moreover, DOTAP at an optimum dose (10 microngram/ml) enhanced IL-12 transgene expression by fivefold in tumor, and twofold in serum after intratumoral injection of adenovirus expressing IL-12N220L (Ad/IL-12N220L). In addition, cotreatment of DOTAP decreased tumor growth rate in the Ad/IL-12N220L-transduced tumor model, finally leading to enhanced survival rate.
CONCLUSION
Our results strongly suggest that DOTAP could be of great utility for improving adenovirus-mediated cancer gene therapy.

Keyword

Adenovirus; DOTAP; liposome; tumor

MeSH Terms

Adenoviridae*
Genes, Neoplasm
Genetic Therapy
Interleukin-12
Liposomes
Propane
Survival Rate
Transgenes
Tropism
Interleukin-12
Liposomes
Propane