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2004 | 51 | 3 | 723-732
Article title

CEA-negative glioblastoma and melanoma cells are sensitive to cytosine deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen promoter.

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EN
Abstracts
EN
Recent studies have suggested that carcinoembryonic antigen (CEA)-promoter sequences are active only in CEA-positive cells, filing in the criteria for tumor specific targeting of suicide genes. However, the present study on gene therapy of colon cancer and cell-specificity of CEA promoter, provide evidence that CEA-positive and CEA-negative cells transfected with E. coli cytosine deaminase (CD) gene under the control of CEA promotor sequence are sensitive to enzyme/pro-drug therapy with 5-fluorocytosine (5-FC). Individual clones derived from the CEA-negative cell lines: melanoma Hs294T and glioblastoma T98G after transfection with CD differed profoundly in their sensitivity to 5-FC. The IC50 values for several clones of the CEA-negative cells were almost the same as for CEA-positive colon cancer cells. Such 5-FC-sensitive clones derived from the population of CEA-negative cells, present even in small number, because of the very effective bystender effect of this enzyme/pro-drug system can cause severe problems during therapy by efficiently killing surrounding normal cells. Safety is the major issue in gene therapy. Our data suggest that the safety of gene-directed enzyme pro-drug therapy (GDEPT) with CEA promoter driven expression of therapeutic genes is not so obvious as it has originally been claimed.
Publisher

Year
Volume
51
Issue
3
Pages
723-732
Physical description
Dates
published
2004
received
2004-02-16
revised
2004-04-21
accepted
2004-05-04
Contributors
  • Faculty of Food Science, Agriculture University, Wrocław, Poland
  • Department of Tumour Biology, Institute of Oncology, Gliwice, Poland
  • Department of Tumour Biology, Institute of Oncology, Gliwice, Poland
  • Department of Tumour Biology, Institute of Oncology, Gliwice, Poland
  • Department of Immunochemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
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Document Type
Publication order reference
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YADDA identifier
bwmeta1.element.bwnjournal-article-abpv51i3p723kz
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