Cloning and characterization of an adenoviral vector for highly efficient and doxycycline – suppressible expression of bioactive human single – chain interleukin 12 in colon cancer |
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| Authors: | Holger Wulff Thorsten Krieger Karen Krüger Ingrid Stahmer Friedrich Thaiss Hansjörg Schäfer Andreas Block |
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| Institution: | (1) Department of Medicine, University of Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany;(2) Department of Immunology, University of Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany;(3) Institute of Pathology, University of Hamburg, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany |
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| Abstract: | Background Interleukin-12 (IL-12) is well characterized to induce cellular antitumoral immunity by activation of NK-cells and T-lymphocytes.
However, systemic administration of recombinant human IL-12 resulted in severe toxicity without perceptible therapeutic benefit.
Even though intratumoral expression of IL-12 leads to tumor regression and long-term survival in a variety of animal models,
clinical trials have not yet shown a significant therapeutic benefit. One major obstacle in the treatment with IL-12 is to
overcome the relatively low expression of the therapeutic gene without compromising the safety of such an approach. Our objective
was to generate an adenoviral vector system enabling the regulated expression of very high levels of bioactive, human IL-12. |
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