Adenovirus-mediated gene transfer into an experimental pancreatic tumour.
OBJECTIVE
Gene therapy has been suggested as a novel approach against pancreatic cancer, a disease with a grim prognosis with current modes of therapy. Despite recent advances in in vitro and experimental in vivo studies, there is no data available concerning gene transfer efficiency in intrapancreatic tumours in immunocompetent animal models.


METHODS
In in vitro studies rat pancreatic carcinoma cells (DSL-6A/C1) were transduced with replication-deficient adenovirus carrying Escherichia Coli beta-galactosidase (lacZ) gene. Gene transfer efficacy was assessed at different multiplicities of infection (MOIs). Pancreatic tumours were induced by inoculating cultured DSL-6A/C1 cancer cells into Lewis rat pancreases. Established tumours were transduced and three days post-transduction, pancreatic tumours as well as other intra-abdominal organs were harvested and processed for histological analyses, including staining for marker gene expression.


CONCLUSIONS
In vitro assays showed that DSL-6A/C1 cells were transduced efficiently, even at low MOIs. In vivo gene transfer was successful in all animals, and all pancreatic samples showed reporter gene expression. Positive cells were detected in the peritumoural areas as well as to a lesser extent within the tumours. The transgene activity was not evenly distributed and the gene transfer efficiency varied from a few detectable blue cells to 11% per field. Our studies demonstrated safe in vivo gene transfer into intrapancreatic tumours, suggesting that pancreatic tumours are potential targets for in vivo delivery of therapeutic genes.
Mäkinen
K
K
Department of Surgery, Kuopio University Hospital, Finland. kimmo.makinen@kuh.fi
Loimas
S
S
Kosma
V M
VM
Wahlfors
J
J
Ylä-Herttuala
S
S
Alhava
E
E
Jänne
J
J
D000260:Adenoviruses, Human; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000628:therapy*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D007121:Immunocompetence; D008297:Male; D010190:Pancreatic Neoplasms / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics*
D001616:beta-Galactosidase