Treatment of metastatic tumors by systemic injection of tumor-retargeted oncolytic herpesviruses

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02687
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Uchida Hiroaki 東京大学, 医科学研究所, 特任准教授 (20401250)
• Co-Investigator(Kenkyū-buntansha): 山口 美樹 札幌医科大学, 医学部, 助教 (10530454) ; 田原 秀晃 東京大学, 医科学研究所, 特任教授 (70322071)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: がん

Outline of Final Research Achievements

The route of administration of oncolytic herpes simplex virus (HSV) in the majority of clinical trials to date has been direct injection into the tumor. This appears to be one of the factors that may limit the therapeutic potential of oncolytic HSV as a single agent against systemically metastatic tumors. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytia formation (RRsyn-oHSV). Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. Intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍の新規治療法として単純ヘルペスウイルスを用いた腫瘍溶解性ウイルス療法が有望視され、本邦を含め広く臨床試験が進められてきたが、その投与経路のほとんどは腫瘍への直接投与の形にとどまっているというのが現状である。がん細胞だけにしか侵入できない標的化ウイルスが開発できれば、ウイルスの増殖能を弱めることなく本来の腫瘍溶解能を最大限に活用した治療戦略が可能となることに加え、これを静脈内投与することにより全身性の転移を来したがん症例を治療することも可能となりうる。本研究の成果は、難治性・転移性のがん症例にも適用可能な腫瘍溶解性ウイルス療法の開発につながり、臨床医学への実用化が大いに期待できる。