Intra-arterial adenoviral mediated tumor transfection in a novel model of cancer gene therapy.
BACKGROUND
The aim of the present study was to develop and characterize a novel in vivo cancer gene therapy model in which intra-arterial adenoviral gene delivery can be characterized. In this model, the rat cremaster muscle serves as the site for tumor growth and provides convenient and isolated access to the tumor parenchyma with discrete control of arterial and venous access for delivery of agents.


RESULTS
Utilizing adenovirus encoding the green fluorescent protein we demonstrated broad tumor transfection. We also observed a dose dependent increment in luciferase activity at the tumor site using an adenovirus encoding the luciferase reporter gene. Finally, we tested the intra-arterial adenovirus dwelling time required to achieve optimal tumor transfection and observed a minimum time of 30 minutes.


CONCLUSIONS
We conclude that adenovirus mediated tumor transfection grown in the cremaster muscle of athymic nude rats via an intra-arterial route could be achieved. This model allows definition of the variables that affect intra-arterial tumor transfection. This particular study suggests that allowing a defined intra-tumor dwelling time by controlling the blood flow of the affected organ during vector infusion can optimize intra-arterial adenoviral delivery.
Cabrera
Gustavo
G
Gene Therapy Laboratory, National Cancer Institute, Mexico City, Mexico. g.cabrera@yahoo.com
Porvasnik
Stacy L
SL
DiCorleto
Paul E
PE
Siemionow
Maria
M
Goldman
Corey K
CK
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007269:Injections, Intra-Arterial; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation / Q000379:methods; D051381:Rats; D011923:Rats, Nude; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases