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KMID : 0617219970080010023
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Duksung Bulletin Phamaceutical Sciences
1997 Volume.8 No. 1 p.23 ~ p.29
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Develoment of an adenoviral vetor system which confers neoplastic cell specific gene expression
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Chung In-Jae
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Abstract
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Replication incompetent adenoviral (Ad) vectors have become widely used for gene replacement strategies in the field of gene therapy. However, one of the limitations of this vector system for cancer gene therapy, in which the Ad is often the carrier of a gene which sensitized cancer cells to chemotherapy, may be non-specific transduction into normal cells. The objective of this study was to develop an Ad vector system which would confer upon the tumor cells the specific expression of exogenous chemotherapy sensitization genes. As a first step, we have generated a recombinant adenoviral vector, Ad.LP.LacZ and tested it in various cell lines for its targeted expression in neoplastic cells. Ad.LP.LacZ is an adenovirus vector containing the transcription unit of the human L-plastin promoter and the E. coli LacZ gene. Infection of Ad.LP.LacZ into the human ovarian carcinoma cell lines, OVCAR-3 and SK-OV-3, or into the human mammary carcinoma cell lines, MDA-MB-436 and MDA-MB-468, or into normal fibroblast cell lines, CCD-862SK and CCD-944SK and the leukemia cell line, HL-60 and U937, showed tumor-specific expression of the LacZ gene driven by the L-plastin promoter. These results suggested that this vector system could be applied to genetic therapy of many types of cancers since the L-plastin promoter is not tissue-but tumor-specific, and would therefore increase the therapeutic index when used with therapeutic genes.
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