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Adenovirus-mediated gene transfer into an experimental pancreatic tumour
K Mäkinen1, S Loimas, V M Kosma
1Department of Surgery, Kuopio University Hospital, Finland. kimmo.makinen@kuh.fi
Background And Aims:
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.
Material And 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.
Results And 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.
Insights
Gene therapy shows promise for pancreatic cancer. This study demonstrated successful and safe in vivo gene transfer into pancreatic tumors in immunocompetent rats, paving the way for new therapeutic strategies.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Pancreatic cancer has a poor prognosis with current treatments.
- Gene therapy offers a potential novel therapeutic approach.
- Data on gene transfer efficiency in immunocompetent models of pancreatic cancer is lacking.
Purpose of the Study:
- To evaluate the efficiency and safety of in vivo gene transfer into intrapancreatic tumors.
- To establish an immunocompetent animal model for pancreatic cancer gene therapy research.
Main Methods:
- Rat pancreatic carcinoma cells (DSL-6A/C1) were transduced with an adenovirus vector carrying the lacZ gene in vitro.
- Intrapancreatic tumors were established in Lewis rats and subsequently transduced.
- Gene transfer efficiency was assessed via histological analysis and marker gene expression (lacZ staining).
Main Results:
- Efficient gene transfer into cancer cells was observed in vitro, even at low multiplicities of infection (MOIs).
- Successful in vivo gene transfer was achieved in all treated pancreatic tumors.
- Reporter gene expression was detected in both peritumoral areas and within tumors, though distribution was uneven.
Conclusions:
- In vivo gene transfer into intrapancreatic tumors is feasible and safe in an immunocompetent model.
- Pancreatic tumors are viable targets for in vivo gene delivery.
- This study provides crucial data for developing gene therapy strategies for pancreatic cancer.