Isolated limb perfusion based anti-p21ras gene therapy in a rat rhabdomyosarcoma

Boudewijn Van Etten, Sandra T. Van Tiel, Gisela Ambagtsheer, Alexander M.M. Eggermont, Timo L.M. Ten Hagen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

5 Citaten (Scopus)


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. 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. 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. 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.

Originele taal-2Engels
Pagina's (van-tot)2295-2301
Aantal pagina's7
TijdschriftAnticancer Research
Nummer van het tijdschrift4
StatusGepubliceerd - jul. 2004
Extern gepubliceerdJa


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