A pilot study of human interferon β gene therapy for patients with advanced melanoma by in vivo transduction using cationic liposomes

Kazuhiko Matsumoto, Hitomi Kubo, Hiroshi Murata, Hisashi Uhara, Minoru Takata, Shinichi Shibata, Satoshi Yasue, Akihiro Sakakibara, Yasushi Tomita, Toshiro Kageshita, Yutaka Kawakami, Masaaki Mizuno, Jun Yoshida, Toshiaki Saida

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)849-856
Number of pages8
JournalJapanese journal of clinical oncology
Volume38
Issue number12
DOIs
Publication statusPublished - 2008

Keywords

  • Clinical trial
  • Gene therapy
  • Interferon β
  • Malignant melanoma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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