Development of oncolytic vaccinia virus with enhanced remote infection capability for ovarian cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Tottori University
• Principal Investigator: KUROSAKI Hajime 鳥取大学, 医学部, 講師 (70464295)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腫瘍溶解性ウイルス / がんウイルス療法 / 抗腫瘍性増強 / 遺伝子改変

Outline of Final Research Achievements

We created a mutant strain capable of producing a large amount of vaccinia virus with enhanced remote infection characteristics, and established a method for functional analysis and evaluation, particularly of morphological characteristics and the ability to evade neutralizing antibodies. A robust purification process and quality control method were established, making it possible to administer to mice a virus with high reproducibility and consistent quality between lots. In vivo studies, we observed increased blood retention and a tendency for infection to spread to tumor sites in tumor-bearing mouse models, suggesting enhanced therapeutic efficacy. We have published a paper on MDRVV, the source of the mutant strain, and are currently working to obtain a patent for the remote infection mutant experiments accumulated in this study and the above-mentioned findings.

Free Research Field

遺伝子治療

Academic Significance and Societal Importance of the Research Achievements

現状の腫瘍溶解性ウイルス療法ではウイルスの全身投与での治療適応は困難とされ、米国で認可された腫瘍溶解性ヘルペスウイルスT-VECも悪性黒色腫への直接投与のみが適応となる。投与部位以外の腫瘍にウイルスを到達させることは困難であり、ウイルスが到達できない腫瘍への治療効果は大きく抑えられることが想定される。しかし、本研究の遠隔感染形質強化型ワクシニアウイルスを用いれば、投与部位の腫瘍組織からEEV形態を産生・放出することで、全身各所の腫瘍に対してもウイルスを到達させその治療効果を発揮することが可能になる。