Combination of Cetuximab and Oncolytic Virus Canerpaturev Synergistically Inhibits Human Colorectal Cancer Growth

• Main Authors: Zhiwen Wu, Toru Ichinose, Yoshinori Naoe, Shigeru Matsumura, Itzel Bustos Villalobos, Ibrahim Ragab Eissa, Suguru Yamada, Noriyuki Miyajima, Daishi Morimoto, Nobuaki Mukoyama, Yoko Nishikawa, Yusuke Koide, Yasuhiro Kodera, Maki Tanaka, Hideki Kasuya
• Format: Article
• Language: English
• Published: Elsevier 2019-06-01
• Series: Molecular Therapy: Oncolytics
• Online Access: http://www.sciencedirect.com/science/article/pii/S237277051930052X

The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro. Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer. Keywords: HSV, cetuximab, oncolytic herpes virus HF10, C-REV, human colorectal cancer