Japanese Journal of Clinical Oncology Advance Access published online on October 22, 2008
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyn114
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© The Author (2008). Published by Oxford University Press. All rights reserved
A Pilot Study of Human Interferon β Gene Therapy for Patients with Advanced Melanoma by in vivo Transduction Using Cationic Liposomes
1 Department of Dermatology, Shinshu University School of Medicine, Matsumoto
2 Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya
3 Department of Dermatology, Faculty of Medicine and Pharmaceutical Science, Kumamoto University, Kumamoto
4 Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo
5 Department of Molecular Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya
6 Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya
7 Clinical Trial Research Center, Shinshu University Hospital, Matsumoto, Japan
For reprints and all correspondence: Kazuhiko Matsumoto, Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. E-mail: climatsu{at}shinshu-u.ac.jp
Received May 30, 2008; accepted September 20, 2008
Background: Cationic liposomes containing the human interferon β (HuIFNβ) gene (IAB-1) was used for the clinical trial for glioma patients. HuIFNβ gene therapy showed much higher anti-tumor activity compared with the administration of HuIFNβ protein for melanoma. These results suggest that HuIFNβ gene therapy is an attractive strategy for the treatment of melanoma.
Methods: Stage IV or III melanoma patients with cutaneous or subcutaneous metastatic lesions were enrolled in this pilot study. IAB-1 was dissolved by sterile PBS at a concentration of 30 µg DNA/ml and was injected into cutaneous or subcutaneous metastatic nodules three times a week for 2 weeks and the effect on the injected and non-injected metastatic lesions was evaluated.
Results: Clinical responses were as follows (five patients): mixed response (MR) and no change in each one patient, and progressive disease in three patients. In the MR patient, the IAB-1 injected lesion disappeared clinically and histopathologically and one-half of IAB-1 non-injected skin metastases were transiently inflamed and mostly regressed. In the responded non-injected lesions of this patient, histopathologically, infiltration of CD4 positive T cells was observed around the melanoma cells in the dermis, which expressed the HLA-Class II antigen. Adverse events due to this gene therapy were not recognized in any of the patients.
Conclusions: The efficacy of this gene therapy was generally insufficient; however, some immunological responses were recognized in one patient. No adverse events were observed. HuIFNβ gene therapy could be an attractive strategy for treatment of a variety of malignancies, including melanoma, though some modifications should be required.
Key Words: interferon β • gene therapy • malignant melanoma • clinical trial