Third-generation oncolytic herpes simplex virus inhibits the growth of liver tumors in mice.

Abstract

Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer treatment. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 kills tumor cells without damaging the surrounding normal tissues. Here we investigated the antitumor effects of T-01 on HCC and the host's immune response to HCC cells. The cytopathic activities of T-01 were tested in 14 human and 1 murine hepatoma cell line in vitro. In various mouse xenograft models, HuH-7, KYN-2, PLC/PRF/5 and HepG2 human cells and Hepa1-6 murine cells were used to investigate the in vivo efficacy of T-01. T-01 was cytotoxic to 13 cell lines (in vitro). In mouse xenograft models of subcutaneous, orthotopic and peritoneal tumor metastasis in athymic mice (BALB/c nu/nu), the growth of tumors formed by the human HCC cell lines and hepatoblastoma cell line was inhibited by T-01 compared with that of mock-inoculated tumors. In a bilateral Hepa1-6 subcutaneous tumor model in C57BL/6 mice, the growth of tumors inoculated with T-01 was inhibited, as was the case for contralateral tumors. T-01 also significantly reduced tumor growth. T-01 infection significantly enhanced antitumor efficacy via T cell-mediated immune responses. Results demonstrate that a third-generation oncolytic HSV-1 may serve as a novel treatment for patients with HCC.

• Authors: Richi Nakatake, Masaki Kaibori, Yusuke Nakamura, Yoshito Tanaka, Hideyuki Matushima, Tadayoshi Okumura, Takashi Murakami, Yasushi Ino, Tomoki Todo, Masanori Kon
• Journal: Cancer science (Cancer Sci) Vol. 109 Issue 3 Pg. 600-610 (Mar 2018) ISSN: 1349-7006 [Electronic] England
• PMID: 29288515 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Topics

• Animals
• Carcinoma, Hepatocellular (immunology, therapy)
• Hep G2 Cells
• Herpesvirus 1, Human (physiology)
• Humans
• Liver Neoplasms (immunology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Oncolytic Viruses (physiology)
• Peritoneal Neoplasms (immunology, secondary, therapy)
• Treatment Outcome
• Virus Replication
• Xenograft Model Antitumor Assays