Interferon-beta gene therapy for cancer: basic research to clinical application.
Interferon-beta gene therapy for cancer is the first such protocol developed in Japan. Here we describe the development process of our interferon-beta gene therapy from basic research to clinical application. Interestingly, the biological and biochemical characteristics of interferon-beta gene therapy through transfer of the interferon-beta gene into tumor cells by means of cationic liposomes differed from those of conventional interferon-beta protein therapy. Interferon-beta gene transfer could induce apoptosis in interferon-beta 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-beta, prolongation of the phosphorylation time of molecules in the interferon-beta signal transduction pathway, such as JAK1, Trk2, and STAT1, and activation of DNase gamma. In our preclinical study we developed lyophilized cationic liposomes containing interferon-beta 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-beta gene therapy. In this review we also comment on the status of gene therapy regulation in Japan. Interferon-beta 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.
Yoshida
Jun
J
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550. jyoshida@med.nagoya-u.ac.jp
Mizuno
Masaaki
M
Wakabayashi
Toshihiko
T
D017209:Apoptosis; D001932:Brain Neoplasms / Q000628:therapy; D004337:Drug Carriers; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000628:therapy; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D016899:Interferon-beta