Efficacy of a Third-Generation Oncolytic Herpes Simplex Virus in Neuroendocrine Tumor Xenograft Models

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10681
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kansai Medical University
• Principal Investigator: ISHIZAKI Morihiko 関西医科大学, 医学部, 講師 (10509467)
• Co-Investigator(Kenkyū-buntansha): 海堀 昌樹 関西医科大学, 医学部, 教授 (30333199) ; 藤堂 具紀 東京大学, 医科学研究所, 教授 (80272566)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 神経内分泌腫瘍 / ウイルス療法

Outline of Final Research Achievements

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.
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.
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.

Free Research Field

外科

Academic Significance and Societal Importance of the Research Achievements

神経内分泌腫瘍は細胞が神経内分泌細胞へ分化・増殖し悪性腫瘍化する疾患で、多くは膵臓や消化管に発生し、肝臓への転移が多い。特にGrade3：NEC（Neuroendocrine Carcinoma）に関しては悪性度が高く予後不良な疾患であり、未だ有効な治療法は確立されていない。抗がん剤の奏功率も低いため有効な治療法の開発が切望される。本研究の結果からNECに対するウイルス療法の効果に期待でき、有効性が確立され今後の臨床応用を目指すことができれば予後改善に繋がる可能性があると考える。