Enhanced in vivo gene delivery to human ovarian cancer xenografts utilizing a tropism-modified adenovirus vector

Recombinant adenovirus vectors are of great interest in the context of cancer gene therapy due to their ability to accomplish efficient in vivo gene transfer. Despite this, however, it should be possible to increase the efficiency of gene transfer by modifying the tropism of adenovirus vectors such that they will bind to receptors which are highly expressed on target cancer cells. To achieve this, the basic fibroblast growth factor (FGF2) was used as a ligand to redirect adenovirus vectors to FGF receptors prevalent on SKOV3.ip1 human ovarian cancer cells. The FGF2 was conjugated to an antibody fragment (Fab), which inhibits adenovirus infection, and the resulting Fab- FGF2 conjugate used to specifically redirect an adenovirus vector carrying the luciferase reporter gene (AdCMVLuc) to SKOV3.ip1 cells in vitro. This analysis demonstrated that Fab-FGF2 modified AdCMVLuc achieved a level of gene expression that was greater than when adenovirus alone was used. More importantly, the Fab-FGF2 conjugate was able to enhance significantly the in vivo expression of the luciferase gene in SKOV3.ip1 tumors implanted intraperitoneally in nude mice. Thus, this work demonstrates that adenovirus vectors can be modified to enhance gene transfer in vivo. Future studies will determine if the efficacy of therapeutic adenovirus vectors can be enhanced using these modifications.