Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft
Gewen Tan, Hideki Kasuya, Tevfik Tolga Sahin, Kazuo Yamamura, Zhiwen Wu, Yusuke Koide, Yoshihiro Hotta, Toshio Shikano, Suguru Yamada, Akiyuki Kanzaki, Tsutomu Fujii, Hiroyuki Sugimoto, Shuji Nomoto, Yoko Nishikawa, Maki Tanaka, Naoko Tsurumaru, Toshie Kuwahara, Saori Fukuda, Toru Ichinose, Toyone Kikumori, Shin Takeda, Akimasa Nakao and Yasuhiro Kodera
Department of Surgery II, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Abstract
Breast cancer is one of the most common and feared cancers faced by women. The prognosis of patients with advanced or recurrent breast cancer remains poor despite refinements in multimodality therapies involving chemotherapeutic and hormonal agents. Multimodal therapy with more specific and effective strategy is urgently needed. The oncolytic herpes simplex virus (HSV) has potential to become a new effective treatment option because of its broad host range and tumor selective viral distribution. Bevacizumab is a monoclonal antibody against VEGFA, which inhibits angiogenesis and therefore tumor growth. Our approach to enhance the antitumor effect of the oncolytic HSV is to combine oncolytic HSV HF10 and bevacizumab in the treatment of breast cancer. Our results showed that bevacizumab enhanced viral distribution as well as tumor hypoxia and expanded the population of apoptotic cells and therefore induced a synergistic antitumor effect. HF10 is expected to be a promising agent in combination with bevacizumab in the anticancer treatment.
Keywords: HSV;bevacizumab;oncolytic herpes virus HF10;angiogenesis inhibitor.