Establishment of virus-free cell substrates for protein drug production

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07853
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Jichi Medical University
• Principal Investigator: Kume Akihiro 自治医科大学, 医学部, 教授 (10264293)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: バイオ医薬品 / 細胞基材 / ウイルス汚染

Outline of Final Research Achievements

The current mainstream of novel drug discovery is rapidly changing from small molecules to biotechnologically produced proteins such as monoclonal antibodies. To produce recombinant proteins, insect cell lines such as Sf9 and High Five have been increasingly favored cell substrates because of their superb efficiency. Recently, however, novel viruses have been discovered as persistent infectants of these cell lines, e.g., SfRV rhabdovirus on Sf9 and TnNV nodavirus on High Five. These findings brought safety concerns on the protein drugs produced with present cell substrates, therefore establishing virus-free insect cells is an urgent issue. Through this study, the researcher successfully removed SfRV from Mimic Sf9, a derivative of Sf9 cells, and established rhabdovirus-free cell lines. The result will aid safer production of recombinant protein drugs for human use.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

医薬品、特にバイオ医薬品の安全性において、原材料から混入しうるウイルスやプリオンなどの感染性因子の問題は常に問題となる重大関心事である。Sf9に感染しているSfRVやHigh Fiveに感染しているTnNVについては、ヒトを含めた哺乳類に対する病原性は知られておらず、ICH-Q5ガイドラインでは「ケースC」として医薬品製造工程で十分なウイルスクリアランスを示せばよいことになっているが、工程内除去はあくまで相対的なものであり、根本的解決とは言い切れない。本課題の成果として得られたウイルスフリー細胞株は、そのような要求に対する答えの一つである。