Abstract
Direct intralesional injection of DNA encoding interferon-α2 (IFN-α2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-α2 using this method resulted in sustained production of IFN-α2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-α protein may therefore be applicable to the treatment of cutaneous BCC.
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Acknowledgements
We thank Ms Nancy Barrett and Ms Donna Gschwend for manuscript preparation and other members of the Nabel laboratory for their helpful advice and comments, and Jon Norman and colleagues at Vical for kindly providing DMRIE/DOPE. MOH is supported by the Commission for the Advancement of Young Scientists and Scholars of the University of Zurich, Switzerland. This work was supported in part by a grant from the National Institutes of Health (1 P01 CA59327).
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Hottiger, M., Dam, T., Nickoloff, B. et al. Liposome-mediated gene transfer into human basal cell carcinoma. Gene Ther 6, 1929–1935 (1999). https://doi.org/10.1038/sj.gt.3301036
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DOI: https://doi.org/10.1038/sj.gt.3301036
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