Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies

作者：Suzawa Ken; Shien Kazuhiko; Peng Huang; Sakaguchi Masakiyo; Watanabe Masami; Hashida Shinsuke; Maki Yuho; Yamamoto Hiromasa; Tomida Shuta; Soh Junichi; Asano Hiroaki; Tsukuda Kazunori; Nasu Yasutomo; Kumon Hiromi; Miyoshi Shinichiro; Toyooka Shinichi^*

来源：Anticancer Research, 2017, 37(1): 301-307.

DOI：10.21873/anticanres.11321

• REIC/DKK3
• gene therapy
• lung cancer
• mesothelioma
• bystander effect

Background: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. Materials and Methods: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. Results: Ad-REIC treatment showed antitumor effect in many lung cancer and malignant mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also of distant untreated tumors. By immunohistochemical analysis, infiltration of T-cells and natural killer (NK) cells and expression of the major histocompatibility complex (MHC) class I molecules were observed in bilateral tumors. Conclusion: Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.

• 出版日期2017-1