Generation of cancer model monkeys and development of novel cancer immunotherapy using regenerated T cells derived from iPS cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22840
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Kondo Kenta 滋賀医科大学, 医学部, 助教 (60779974)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: カニクイザル / 癌免疫療法 / iPS細胞 / 再生T細胞 / TCR

Outline of Final Research Achievements

To create a non-human primate cancer model, we tried to generate monkeys that express four cancer-related genes in a drug-inducible manner: p53CT, a dominant mutant that inhibits p53; CDK4, which inhibits the Rb pathway; activated KRAS (G12V); and telomerase reverse transcriptase TERT. We succeeded in obtaining the transgenic non-human primate. In addition, we isolated TCR genes from T cells infiltrated in tumor cells transplanted from monkeys and introduced them into regenerated T cells from iPS cells. We found that these TCR-transduced regenerated T cells kill the tumor cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法の前臨床試験において、マウスで得られた知見がヒトに外挿できない例が知られている。そのためヒトへの外挿性が高い霊長類を用いたがん研究が必要不可欠である。本研究で作製された遺伝子導入サルで薬剤誘導性に腫瘍が形成されれば、世界初の非ヒト霊長類のがんモデルとなり、霊長類を用いたがん免疫療法の前臨床試験が可能になる