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

Details

Serval ID
serval:BIB_7ED5E015E7B4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intralesional adenovirus-mediated interleukin-2 gene transfer for advanced solid cancers and melanoma.
Journal
Molecular Therapy
Author(s)
Dummer R., Rochlitz C., Velu T., Acres B., Limacher J.M., Bleuzen P., Lacoste G., Slos P., Romero P., Urosevic M.
ISSN
1525-0024 (Electronic)
ISSN-L
1525-0016
Publication state
Published
Issued date
2008
Volume
16
Number
5
Pages
985-994
Language
english
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.
Keywords
Adenoviridae/genetics, Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell/genetics, Carcinoma, Squamous Cell/therapy, Dacarbazine/pharmacology, Female, Gene Therapy/methods, Gene Transfer Techniques, Genetic Vectors, Humans, Interleukin-2/genetics, Interleukin-2/metabolism, Male, Melanoma/genetics, Melanoma/therapy, Middle Aged, Neoplasm Metastasis
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2011 9:07
Last modification date
20/08/2019 14:39
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