Abstract
Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope ; HVJ-E) are safe and efficient nonviral vectors for drug delivery as they can incorporate DNA, RNA, proteins, and drugs. We have recently found a novel antitumor immunity of HVJ-E using a colon cancer model. Moreover, intratumoral injection of inactivated HVJ-E solution significantly reduces tumor volume and prevents the occurrence of lung metastasis, conducive to extending overall survival in C57/BL6 mice transplanted with B16/F10 mouse melanoma cells and even immunodeficient mice transplanted with MeWo human melanoma cells. In contrast, no severe adverse events including laboratory data abnormality and anaphylactic reaction were observed. The comprehensive mechanisms of immunologic effect by HVJ-E appear to include not only enhanced effector T cell-and/or NK cell-mediated immunity but also rescue from regulatory T cell (Treg)-mediated immunosuppression, presumably through IL-6 secretion from dendritic cells stimulated by HVJ-E. Since the protocol of this clinical study in malignant melanoma was recently approved by the ethical committee of Osaka University and by the Medical Center for Translational Research in Osaka University Hospital, a phase I/II study for advanced malignant melanoma patients has just started. In this review, we show several favorable results regarding the antitumor effect of HVJ-E and mention the mechanism of this immunity. In addition, we introduce the selection/exclusion criteria and schedule for phase I/II clinical trial.[Skin Cancer (Japan) 2009 ; 24 : 181-191]
