Clinical Efficacy by Intratumoral Injection of DNA Encoding Human Interleukin-12 in Metastatic Melanoma Patients

Karin Moelling ,Lina Elzaouk ,Jovan Pavlovic ,Lucie Heinzerling

doi:10.1186/1742-4690-2-s1-p131

Abstract

Plasmid DNA encoding human Interleukin-12 (IL-12) was produced under GMP conditions and injected into lesions of nine patients with malignant melanoma (stage IV) previously treated with both, standard and non-standard therapies. The treatment was based on efficacy in preclinical studies with melanoma in mice and gray horses. The DNA was applied in cycles, three injections per cycle, up to seven cycles. Three therapy arms comprised low (2 mg), medium (4 mg) and high (10 to 20 mg) amounts of total DNA. The therapy was well tolerated. Three out of nine patients experienced a clinical response, 2 SD and 1 CR. One patient receiving a low dose of DNA experienced a long-lasting stabilization of the disease for more than three years, while the other two responders received high doses of DNA. All patients but one (P9) experienced a transient response at the intratumoral injection site. Immunohistochemical staining of responders showed local reduction of angiogenesis and lymphocyte infiltrations. All patients, in particular the responders (P3, P7, and P8) exhibited an antigen-specific immune response against MAGE-1 and MART-1. Biopsies of responders showed some increase of IL-12, IP-10 and IFN-γ. (Hu. Gene Ther. 16, 35 (2005)). Combinations of IL-12 DNA with other therapies show significant increase of efficacy in preclinical studies and will be discussed. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005

Highlights

national Meeting of The Institute of Human Virology Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here. [link 'here' using 'a href' to: http://www.biomedcentral.com/content/pdf/1742-4690-2-S1
The treatment was based on efficacy in preclinical studies with melanoma in mice and gray horses
The DNA was applied in cycles, three injections per cycle, up to seven cycles

Summary

Introduction

Clinical Efficacy by Intratumoral Injection of DNA Encoding Human K Moelling*‡1, J Pavlovic1, L Elzaouk1 and L Heinzerling2 et al Address: 1Institute of Medical Virology, University of Zurich, Switzerland and 2Department of Dermatology, University of Zurich, Switzerland Email: K Moelling* - moelling@immv.unizh.ch * Corresponding author ‡Presenting author from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005

Results

Conclusion