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Isolated limb perfusion based anti-p21ras gene therapy in a rat rhabdomyosarcoma.
- Source :
-
Anticancer research [Anticancer Res] 2004 Jul-Aug; Vol. 24 (4), pp. 2295-301. - Publication Year :
- 2004
-
Abstract
- Background: Inhibition of ras oncogene is a promising new strategy. Gene therapy against ras proved successful in human and murine tumour cell lines. Previously we demonstrated effective targeted transfection of tumour in a rat model by using an isolated limb perfusion (ILP) for the delivery of adenoviral vectors.<br />Materials and Methods: This study explores the anti-tumour activity of an adenoviral construct encoding an intracellular single-chain antibody (scFv) against p21ras (Y28). In order to determine the influence of the ras status on the efficacy of the scFv, we used a wild-type rat rhabdomyosarcoma and its ras-oncogene transfectant, for in vitro studies. In vivo we used the ILP delivery method to study anti-tumour activity on established limb tumours.<br />Results: In vitro studies demonstrated an inhibition of growth caused by the Y28 construct. No significant difference between transfected and wild-type cell lines could be demonstrated. Upon ILP, homogeneous transduction was observed in 5% of tumour cells. Perfusion with the Y28 construct, however, did not result in any additional anti-tumour activity compared to controls.<br />Conclusion: Despite in vitro activity and in vivo transfection, no significant tumour response could be detected using anti-p21ras gene therapy in this ILP-tumour model.
- Subjects :
- Adenoviridae genetics
Animals
Antibody Specificity
Cell Line, Tumor
Chemotherapy, Cancer, Regional Perfusion
Genes, ras genetics
Genetic Vectors administration & dosage
Genetic Vectors genetics
Immunoglobulin Fragments genetics
Immunoglobulin Fragments immunology
Rats
Rhabdomyosarcoma genetics
Transfection
Genetic Therapy methods
Proto-Oncogene Proteins p21(ras) genetics
Rhabdomyosarcoma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 15330175