Institutional members access full text with Ovid®

Double-blind Placebo-controlled Study With Interleukin-18 and Interleukin-12-encoding Plasmid DNA Shows Antitumor Effect in Metastatic Melanoma in Gray Horses

Müller, Jessika- M.V.*; Feige, Karsten*; Wunderlin, Patrizia; Hödl, Andreas; Meli, Marina L.§; Seltenhammer, Monika; Grest, Paula; Nicolson, Lesley; Schelling, Claude**; Heinzerling, Lucie M.††,‡‡

doi: 10.1097/CJI.0b013e3181fe1997
Basic Studies

Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, or empty plasmid DNA (control group), injected intratumorally, respectively. Tumor response was assessed using ultrasound and caliper measurements and histologic assessment of tumor biopsies. Significant tumor regression could be shown in both the treatment groups receiving IL-18 and IL-12-encoding plasmid DNA whereas placebo-treated control patients showed tumor growth over the course of the treatment. In addition, 7 of 10 tumors from horses treated with IL-18 or IL-12 showed peritumoral and/or intratumoral inflammatory infiltrates after treatment compared with 1 of the 6 in the control group. The treatment as assessed by serial blood draws and clinical investigation, was safe and well tolerated. These data suggest that the intratumoral treatment with IL-18 and IL-12-encoding plasmid DNA has antitumor effects, which is well tolerated and thus holds promise for the treatment of patients with metastatic melanoma.

*Clinic for Horses, University of Veterinary Medicine Hannover, Hannover

‡‡University Hospital, Berlin, Germany

Equine Clinic

§Clinical Laboratory

Department of Pathology, Vetsuisse Faculty University of Zurich

**Animal Genetics Group, Vetsuisse Faculty Zurich and Department of Animal Sciences, Swiss Federal Institute of Technology, Zurich

††Department of Dermatology and Allergy, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Department of Clinical Surgery and Ophthalmology, University of Veterinary Medicine, Vienna, Austria

Nottingham University Hospital, NHS Treatment Centre, Queens Medical Centre Campus, Nottingham

Division of Infection and Immunity, Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Glasgow, UK

All authors have declared that there are no financial conflicts of interest in regards to this work.

The study was financially supported by the research commission of the University of Zurich with resources from the research credit 2003.

Animals were treated at two study centers: at the University of Zurich Equine Clinic, University of Zurich (n=20), and at the Clinic for Surgery and Ophthalmology at the Veterinary University of Vienna (n=6).

Reprints: Lucie M. Heinzerling, Department of Dermatology and Allergy, Cantonal Hospital St. Gallen, Rorschacherstr. 95, 9007 St. Gallen, Switzerland (e-mail: lheinzer@post.harvard.edu).

Received June 8, 2010

Accepted August 31, 2010

© 2011 Lippincott Williams & Wilkins, Inc.