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Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model

Gene Therapy volume 10, pages 206–212 (2003)Cite this article

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.

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Authors and Affiliations

  1. Department of Surgery, The University of Chicago, Chicago, IL, USA

    V K Gupta, J O Park, N T Jaskowiak & M C Posner

  2. Division of Pharmacology, Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA

    T Kurihara & D W Kufe

  3. Department of Radiation and Cellular Oncology, Chicago, IL, USA

    A Koons, H J Mauceri & R R Weichselbaum

Authors
  1. V K Gupta
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  2. J O Park
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  3. T Kurihara
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  4. A Koons
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  5. H J Mauceri
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  6. N T Jaskowiak
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  7. D W Kufe
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  8. R R Weichselbaum
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  9. M C Posner
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Gupta, V., Park, J., Kurihara, T. et al. Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model. Gene Ther 10, 206–212 (2003). https://doi.org/10.1038/sj.gt.3301867

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