Summary
An ideal cancer gene therapy would selectively kill cancer cells without harming normal cells and induce potent anti-tumor immunity, facilitating eradication of both primary and metastatic tumors. The REIC/Dkk-3（reduced expression in immortalized cells/Dickkopf-3）was isolated at Okayama University (BBRC 2000; 268:20) and found to be a new tumor suppressor gene (Cancer Res.2005; 65:9617). Inventors’ research group demonstrated that its forced expression using adenoviral vector (Ad-REIC) induces cancer selective apoptosis and potent anti-tumor immunity. Momotaro-Gene Inc.＜http://www.mt-gene.com＞, who is an Okayama University-based start-up company, manufactured a GMP-grade medical product of Ad-REIC. Okayama University has conducted its clinical study for prostate cancer and also currently applied for another clinical study for malignant mesothelioma. In addition, Momotaro-Gene Inc. has been manufacturing another GMP-grade medical product of Ad-SGE-REIC which is ten times more effective than the current one and they will start clinical study for prostate cancer in the US in 2013.
Advantages
1. Cancer selective apoptosis They have revealed the mechanism of cancer selective apoptosis. The expression of REIC is significantly reduced in a wide variety of cancer cells and its forced expression using adenoviral vector (Ad-REIC) induces cancer selective apoptosis through the activation of JNK-c-jun pathway due to endoplasmic reticulum (ER) stress (Cancer Res. 2008; 68:8333）. Even a certain REIC gene fragment also induces this cancer selective apoptosis via ER stress.
2. Anti-tumor immunostimulant capability Studies using recombinant REIC protein revealed its immunological role in monocyte differentiation into a dendritic-cell phenotype and in vivo tumor regression （Int’l J. Oncol. 2009; 34:657）. In addition, its overexpression in normal fibroblasts suppresses tumor growth via induction of interleukin-7, providing an indirect host-mediated effect on cancer cells (J. Biol. Chem. 2009; 284:14236). Local and systemic ‘bystander’ anti-tumor effects generated by in situ Ad-REIC gene therapy were confirmed in orthotopic animal models using prostate cancer and malignant mesothelioma cells.
Inventors
Prof. Hiromi KUMON (Okayama University, Japan), et al.
Product No: TP0230