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
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 10:07
Last modification date
20/08/2019 15:39