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Cancer Science logoLink to Cancer Science
. 2005 Aug 19;95(11):858–865. doi: 10.1111/j.1349-7006.2004.tb02194.x

lnterferon‐β gene therapy for cancer: Basic research to clinical application

Jun Yoshida 1,, Masaaki Mizuno 2, Toshihiko Wakabayashi 1
PMCID: PMC11158352  PMID: 15546502

Abstract

Interferon‐β gene therapy for cancer is the first such protocol developed in Japan. Here we describe the development process of our interferon‐β gene therapy from basic research to clinical application. Interestingly, the biological and biochemical characteristics of interferon‐β gene therapy through transfer of the interferon‐(gene into tumor cells by means of cationic liposomes differed from those of conventional interferon‐β protein therapy. Interferon‐β gene transfer could induce apoptosis in interferon‐β protein‐resistant tumor cells, such as glioma, melanoma, and renal cell carcinoma. Induction of apoptosis was related to the level of intracellular mRNA of interferon‐β, prolongation of the phos‐phorylation time of molecules in the interferon‐p signal transduc‐tion pathway, such as JAK1, Trk2, and STAT1, and activation of DNase γ. In our preclinical study we developed lyophilized cat‐ionic liposomes containing interferon‐β gene (gene drug) for clinical use and confirmed their safety. Thereafter, we performed a pilot clinical trial in patients with malignant glioma and confirmed the safety and effectiveness of this interferon‐β gene therapy. In this review we also comment on the status of gene therapy regulation in Japan. Interferon‐β gene therapy is expected to become widely available for clinical use in cancer patients, and this new strategy might be extended to molecular targeting therapy, or used in combination with cell therapy or other therapies.

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