Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model
- 23 January 2003
- journal article
- Published by Springer Nature in Gene Therapy
- Vol. 10 (3) , 206-212
- https://doi.org/10.1038/sj.gt.3301867
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- in the same DF3-producing cells. We also show that the increased TNF- 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- provides a novel approach to enhancing tumor radiosensitivity.Keywords
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