Abstract
Suicide gene therapy is an attractive way of combating cancers. Diphtheria toxin (DT) has been widely studied for its application to kill cancer cells. Due to DT's extreme toxicity issue, viral vectors carrying DT are very difficult to produce since producer cells are killed before viral vectors can be produced. In this study adeno-associated viral (AAV) vectors carrying DT fragment A (DT-A) was generated at high titers in insect cells by inserting a mammalian intron to abolish the toxin expression. When these toxin carrying AAV vectors were introduced into mammalian cells, the intron was spliced out and the toxin expressed and killed the mammalian cells. Since they can direct gene expression in tumor cells but not in normal cells, tumor-specific promoters were cloned to direct the expression of the DT-A gene and AAV vectors were prepared. These vectors carrying DT-A under control of surviving or CXCR4 promoter specifically killed tumor cell lines HepG2, Hep3B, and BE (2)-M17, but not the normal human lung cell line WI38. The results in this study indicate that this novel way of targeting tumor cells with AAV vectors carrying DT-A should provide a new tool for the development of toxin-based suicide gene therapy drugs.
Citation Format: Haifeng Chen. Transcriptional targeting of tumor cells with AAV vectors carrying diphtheria toxin A fragment. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B36.
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