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Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma

Dummer, R. and Rochlitz, C. and Velu, T. and Acres, B. and Limacher, J. M. and Bleuzen, P. and Lacoste, G. and Slos, P. and Romero, P. and Urosevic, M.. (2008) Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma. Molecular therapy, Vol. 16, H. 5. pp. 985-994.

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Official URL: http://edoc.unibas.ch/dok/A6007136

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Abstract

Numerous preclinical and clinical studies have shown that interleukin-2 (IL-2) induces regression of metastatic tumors. We have conducted a phase I/II, multicenter, open-label, dose-escalating study to evaluate the safety, efficacy, and biological effects of repeated intratumoral injections of adenovirus-IL-2 (TG1024) in patients with advanced solid tumors and melanoma. Thirty five patients (twenty-five with metastatic melanoma and ten with other solid tumors) were treated in eight successive cohorts at dose levels ranging from 3 x 10(8) to 3 x 10(11) viral particles (vp). Intratumoral TG1024 injections in combination with dacarbazine (DTIC) were tested in metastatic melanoma in one cohort. No clinical responses were observed at doses below 3 x 10(11) vp. Six local objective responses were recorded in patients receiving 3 x 10(11) vp per treatment [five in metastatic melanoma and one in metastatic squamous cell carcinoma (SCC) of the skin], of which two were complete responses (CRs). Most of the common side effects were injection site reactions and flu-like syndrome. TG1024 dose intensification across cohorts resulted in increased serum IL-2 levels after the injection. Intratumoral TG1024 injection induced pronounced inflammation of the treated lesion, with predominant CD8(+), TIA+ lymphocytic infiltrate. Our results show that intratumoral injections of TG1024 are safe and well tolerated. The clinical activity of TG1024 observed in this study warrants further investigations.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cancer Immunology and Biology (Zippelius/Rochlitz)
UniBasel Contributors:Rochlitz, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Academic Press
ISSN:1525-0016
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:23
Deposited On:24 May 2013 09:20

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