The nitroreductase/CB1954 combination in Epstein-Barr virus-positive B-cell lines: Induction of bystander killing in vitro and in vivo
- 1 January 2000
- journal article
- research article
- Published by Springer Nature in Cancer Gene Therapy
- Vol. 7 (1) , 97-106
- https://doi.org/10.1038/sj.cgt.7700102
Abstract
Epstein-Barr virus (EBV)-based gene delivery vectors that preferentially express toxic genes in EBV-infected cells could be used to target EBV-positive tumors for destruction. We have shown previously that the cytosine deaminase (CD) enzyme, which converts the prodrug 5-fluorocytosine (5-FC) into the toxic compound 5-fluorouracil efficiently kills EBV-positive cells in the presence of 5-FC, with a substantial bystander killing effect in vitro and in vivo. To identify the optimal enzyme/prodrug combination for treating EBV-positive lymphomas, we have compared the effectiveness of the CD/5-FC combination with the nitroreductase (NTR)/CB1954 combination for killing EBV-positive B-cell lines. NTR metabolizes CB1954 into an alkylating agent that cross-links DNA. When the CD gene or the NTR gene were transfected into two different EBV-positive B-cell lines in vitro, ∼ 90% of cells were killed in a prodrug-dependent manner, although the transfection efficiency was in vitro but may not be as effective as the CD/5-FC combination for treating B-cell lymphomas in vivo.Keywords
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