Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor

Corey K. Goldman, Buck E. Rogers, Joanne T. Douglas, Barbara A. Sosnowski, Wenbin Ying, Gene P. Siegal, Andrew Baird, Julie A. Campain, David T. Curiel

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161 Scopus citations

Abstract

Kaposi's sarcoma (KS) is a major AIDS-related malignancy associated with significant morbidity and mortality. Current chemotherapeutic regimens are associated with a dismal prognosis. In an effort to develop a new approach to KS treatment, we devised a gene therapy-based adenovirus retargeting schema that redirects the adenovirus to fibroblast growth factor receptors endogenously present on the cell surface of KS cells. By using a bifunctional conjugate consisting of a blocking antiadenoviral knob Fab linked to basic fibroblast growth factor, FGF2, the gene transduction of KS cells was enhanced 7.7-44 fold; recombinant adenoviruses encoding either the firefly luciferase reporter gene, or the herpes simplex thymidine kinase gene, demonstrated quantitative enhancement of expression in the KS cell lines. In this regard, two KS cell lines that were previously refractory to native adenovirus transduction could be successfully transduced by the addition of the conjugate. This study thus addresses the utility of adenoviral retargeting to the FGF receptor in KS cells that are ordinarily transduction refractory to standardized approaches and allows practical development of gene therapy approaches for the treatment of human KS.

Original languageEnglish
Pages (from-to)1447-1451
Number of pages5
JournalCancer research
Volume57
Issue number8
StatePublished - May 6 1997
Externally publishedYes

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    Goldman, C. K., Rogers, B. E., Douglas, J. T., Sosnowski, B. A., Ying, W., Siegal, G. P., Baird, A., Campain, J. A., & Curiel, D. T. (1997). Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor. Cancer research, 57(8), 1447-1451.