Lokale nicht-virale Gentherapie in kutanen Metastasen von Mammakarzinom und Melanom: Ergebnisse einer Phase-I-Studie mittels Jet-Injektion nackter DNA

Item Type:	Article
Title:	Lokale nicht-virale Gentherapie in kutanen Metastasen von Mammakarzinom und Melanom: Ergebnisse einer Phase-I-Studie mittels Jet-Injektion nackter DNA
Creators Name:	Siegel, R. and Kobelt, D. and Knoesel, T. and Stein, U. and Schlag, P.M. and Walther, W.
Abstract:	Background: This phase I clinical trial evaluated safety, feasibility and efficiency of nonviral intratumoral jet-injection reporter gene transfer in patients with skin metastases frommelanoma and breast cancer. Methods: Seventeen patients were enrolled. The patients received five jet-injections of beta-galactosidase (LacZ) expressing plasmid-DNA (pCMVbeta) into a single cutaneous lesion. Clinical and laboratory safety monitoring were performed and systemic plasmid clearance was monitored by quantitative real-time PCR (qPCR) of blood samples throughout the study. All lesions were resected after two to six days. Intratumoral plasmid DNA-load, DNA-distribution and LacZ-expression was analyzed by qPCR, quantitative RT-PCR,Western-blot, immunohistochemistry and X-gal staining. Results: Jet-injection of plasmid-DNAwas safely performedin all patients.No serious side effectswere observed. Thirty minutes after jet-injection peak plasmid-DNA levels were detected in the blood followed by rapid decline and clearance. Plasmid-DNA, LacZ mRNA- and protein expression were detected in all treated lesions. Quantitative analysis revealed a correlation of plasmid-DNA load and LacZ-mRNA expression, confirmed by Western-blot. Immunohistochemistry and X-gal staining demonstrated LacZ-protein throughout the tumor. Transfected tumor areas were found close and distant to the jet-injection site with varying levels ofDNA-load and transgene expression. Conclusion: Intratumoral jet-injection of plasmid-DNA led to an efficient LacZ-reporter gene expression in all patients. No side effects were experienced, supporting safety and applicability of this novel nonviral approach. Based on these results a next step with a therapeutic gene product should determine antitumor efficacy of jet-injection gene transfer.
Source:	Chirurgisches Forum 2008
Series Name:	Deutsche Gesellschaft für Chirurgie
Title of Book:	Chirurgisches Forum 2008 fuer experimentelle und klinische Forschung 125. Kongress der Deutschen Gesellschaft fuer Chirurgie Berlin, 22.04. - 25.04.2008
ISSN:	1432-9336
ISBN:	978-3-540-78821-8
Publisher:	Springer
Volume:	37
Page Range:	131-132
Number of Pages:	342
Date:	2008
Official Publication:	https://doi.org/10.1007/978-3-540-78833-1_48

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