In Vivo Gene Therapy for α-Fetoprotein-producing Hepatocellular Carcinoma by Adenovirus-mediated Transfer of Cytosine Deaminase Gene

摘要: Abstract The α-fetoprotein ( AFP ) gene is normally expressed in fetal liver and transcriptionally silent adult but overexpressed human hepatocellular carcinoma (HCC). Here, we demonstrate that replication defective recombinant adenoviral vectors, containing the promoter/enhancer, can be used to express Escherichia coli cytosine deaminase CD AdAFPCD β-galactosidase AdAF-PlacZ AFP-producing HCC cell lines. Expression of by adenovirus from promoter/enhancer induced cells sensitive 5-fluorocytosine (5FC) not AFP-nonproducing cells. Transduction an vector harboring ubiquitous strong promoter showed enzymatic activity 5FC killing all When AdAFPlacZ was injected into s.c. established hepatoma vivo , expression confined xenografts. Moreover, xenografts regressed transduction with subsequently treatment . These findings suggest utilization confer selective a heterologous suicide vitro