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Title: Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum
Authors: Theys, Jan ×
Landuyt, W
Nuyts, Sandra
Van Mellaert, Lieve
Van Oosterom, Allan
Lambin, Philippe
Anné, Jozef #
Issue Date: Apr-2001
Series Title: Cancer gene therapy vol:8 issue:4 pages:294-7
Abstract: The presence of severe hypoxia and necrosis in solid tumors offers the potential to apply an anaerobic bacterial enzyme/prodrug approach in cancer treatment. In this context the apathogenic C. acetobutylicum was genetically engineered to express and secrete E. coli cytosine deaminase (CDase). Considerable levels of functional cytosine deaminase were detected in lysates and supernatants of recombinant C acetobutylicum cultures. After administration of the recombinant Clostridium to rhabdomyosarcoma bearing rats used as a model, cytosine deaminase could be detected at the tumor site. Moreover, following administration of the vascular targeting agent combretastatin A-4 phosphate significantly increased levels of cytosine deaminase were detected at the tumor site as a consequence of enlarged tumor necrosis and subsequently improved growth of C. acetobutylicum. The results provide evidence for the potential application of Clostrisdium-based therapeutic protein transfer to tumors in anticancer therapy.
ISSN: 0929-1903
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Oncology - miscellaneous
Laboratory of Molecular Bacteriology (Rega Institute)
Laboratory of Experimental Radiotherapy
× corresponding author
# (joint) last author

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