Oncotarget

Research Papers:

Efficacy of a third-generation oncolytic herpes simplex virus in neuroendocrine tumor xenograft models

Hideyuki Matsushima, Masaki Kaibori _, Masahiko Hatta, Morihiko Ishizaki, Richi Nakatake, Tadayoshi Okumura, Kengo Yoshii and Tomoki Todo

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Oncotarget. 2019; 10:7132-7141. https://doi.org/10.18632/oncotarget.27391

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Abstract

Hideyuki Matsushima1, Masaki Kaibori1, Masahiko Hatta1, Morihiko Ishizaki1, Richi Nakatake1, Tadayoshi Okumura1,2, Kengo Yoshii3 and Tomoki Todo4

1 Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan

2 Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan

3 Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan

4 Division of Innovative Cancer Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan

Correspondence to:

Masaki Kaibori,email: [email protected]

Keywords: oncolytic virus; herpes simplex virus; neuroendocrine tumor; mouse xenograft model

Received: August 22, 2019     Accepted: December 02, 2019     Published: December 24, 2019

ABSTRACT

BACKGROUND: Few chemotherapies are available for neuroendocrine tumors, especially for highly malignant neuroendocrine cancers. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 selectively replicates in tumor cells and shows cytotoxicity against tumor cells without damaging surrounding normal tissues. We examined the antitumor effect of T-01 to explore novel treatments for patients with neuroendocrine tumors.

METHODS: The cytotoxicity of T-01 was tested in two human and one murine neuroendocrine tumor cell lines in vitro. Mouse models with subcutaneously implanted human neuroendocrine tumor QGP1 cells were used to investigate T-01 efficacy in vivo.

RESULTS: T-01 showed cytotoxicity against the three cell lines in vitro. In xenograft models, the growth of tumors derived from QGP1 cells was inhibited by T-01 compared with control group. Although weight loss of mice was observed with tumor growth in the control group, it was suppressed by T-01 administration. The antitumor effects of T-01 were dependent on virus concentration and frequency of administration.

CONCLUSIONS: T-01 effectively inhibits tumor cell proliferation in a poorly differentiated NEC mouse model. These results suggest that the third-generation oncolytic HSV-1 may serve as a novel treatment for patients with neuroendocrine tumors.


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