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Youn, Jin, and Sung: Enhancement of Transduction Efficiency and Antitumor Effects of IL-12N220L-expressing Adenovirus by Co-delivery of DOTAP
Original Article

Immune Network 2007; 7(4): 179-185.

Published online: 31 December 2007

DOI: https://doi.org/10.4110/in.2007.7.4.179

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

Je-In Youn1, Hyun-Tak Jin2, Young-Chul Sung1

1Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea.

2Research Institute, Genexine Co. Ltd., Pohang, Korea.

Correspondence to: Young-Chul Sung, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja-dong, Pohang 790-784, Korea. (Tel) 82-54-279-2294, (Fax) 82-54-279-5544, ycsung@postech.ac.kr

Copyright © 2007 The Korean Association of Immunologists

(open-access):

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 µg/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.

Keywords: Adenovirus, DOTAP, liposome, tumor

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