RRC ID 56151
著者 Nakatake R, Kaibori M, Nakamura Y, Tanaka Y, Matushima H, Okumura T, Murakami T, Ino Y, Todo T, Kon M.
タイトル Third-generation oncolytic herpes simplex virus inhibits the growth of liver tumors in mice.
ジャーナル Cancer Sci
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.
巻・号 109(3)
ページ 600-610
公開日 2018-3-1
DOI 10.1111/cas.13492
PMID 29288515
PMC PMC5834814
MeSH Animals Carcinoma, Hepatocellular / immunology Carcinoma, Hepatocellular / therapy* Hep G2 Cells Herpesvirus 1, Human / physiology* Humans Liver Neoplasms / immunology Liver Neoplasms / therapy* Mice Mice, Inbred BALB C Mice, Inbred C57BL Oncolytic Viruses / physiology* Peritoneal Neoplasms / immunology Peritoneal Neoplasms / secondary Peritoneal Neoplasms / therapy* Treatment Outcome Virus Replication Xenograft Model Antitumor Assays
IF 4.751
引用数 6
リソース情報
ヒト・動物細胞 Vero(RCB0001)