Chimeric adenoviral vectors incorporating a fiber of human adenovirus 3 efficiently mediate gene transfer into prostate cancer cells.
BACKGROUND
We have developed a range of adenoviral (Ad) vectors based on human adenovirus serotype 5 (HAdV-5) displaying the fiber shaft and knob domains of species B viruses (HAdV-3, -11, or -35). These species B Ads utilize different cellular receptors than HAdV-5 for infection. We evaluated whether Ad vectors displaying species B fiber shaft and knob domains (Ad5F3Luc1, Ad5F11Luc1, and Ad5F35Luc1) would efficiently infect cancer cells of distinct origins, including prostate cancer.


METHODS
The fiber chimeric Ad vectors were genetically generated and compared with the original Ad vector (Ad5Luc1) for transductional efficiency in a variety of cancer cell lines, including prostate cancer cells and primary prostate epithelial cells (PrEC), using luciferase as a reporter gene.


RESULTS
Prostate cancer cell lines infected with Ad5F3Luc1 expressed higher levels of luciferase than Ad5Luc1, as well as the other chimeric Ad vectors. We also analyzed the transductional efficiency via monitoring of luciferase activity in prostate cancer cells when expressed as a fraction of the gene transfer in PrEC cells. In the PC-3 and DU145 cell lines, the gene transfer ratio of cancer cells versus PrEC was once again highest for Ad5F3Luc1.


CONCLUSIONS
Of the investigated chimeric HAdV-5/species B vectors, Ad5F3Luc1 was judged to be the most suitable for targeting prostate cancer cells as it showed the highest transductional efficiency in these cells. It is foreseeable that an Ad vector incorporating the HAdV-3 fiber could potentially be used for prostate cancer gene therapy.
Murakami
Miho
M
Division of Human Gene Therapy, Department of Medicine, Obstetrics and Gynecology, Pathology, Surgery, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Ugai
Hideyo
H
Belousova
Natalya
N
Pereboev
Alexander
A
Dent
Paul
P
Fisher
Paul B
PB
Everts
Maaike
M
Curiel
David T
DT
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D036022:Capsid Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy; D011993:Recombinant Fusion Proteins; D014161:Transduction, Genetic
D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; C018315:hexon capsid protein, Adenovirus