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- Title
Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model.
- Authors
Gupta, V K; Park, J O; Kurihara, T; Koons, A; Mauceri, H J; Jaskowiak, N T; Kufe, D W; Weichselbaum, R R; Posner, M C
- Abstract
The efficacy of replication-deficient adenoviral vectors in gene therapy is confined to the number of tumor cells the vector infects. To focus and enhance the therapeutic efficacy, we employed a conditionally replication-competent adenoviral vector with a tissue-specific promoter, DF3/MUC1, in a human esophageal adenocarcinoma model. Our results demonstrate that Ad.DF3.E1A.CMV.TNF (Ad.DF3.TNF) specifically replicates in Bic-1 (DF3-producing cells) and mediates an enhanced biologic effect due to increased TNF-α in the same DF3-producing cells. We also show that the increased TNF-α interacts with ionizing radiation to produce greater tumor regression and a greater delay in tumor regrowth in Bic-1 (DF3-producing cells) compared to Seg-1 (DF3 non-producers). Tumor cell targeting using conditionally replication-competent adenoviral vectors with tumor-specific promoters to drive viral replication and deliver TNF-α provides a novel approach to enhancing tumor radiosensitivity.Gene Therapy (2003) 10, 206–212. doi:10.1038/sj.gt.3301867
- Subjects
GENE expression; GENE therapy; TREATMENT of esophageal cancer
- Publication
Gene Therapy, 2003, Vol 10, Issue 3, p206
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301867