Establishment of a fail-safe system in cardiac regenerative medicine using CAR-T cell therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16082
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Keio University
• Principal Investigator: Okada Marina 慶應義塾大学, 医学部(信濃町), 助教 (00594582)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: CAR-T細胞療法 / 心筋細胞移植 / 未分化細胞除去 / iPS細胞 / 奇形腫形成抑制

Outline of Final Research Achievements

We completed the production of monoclonal antibody against GPC3, the production of chimeric antigen receptor (CAR) by gene modification, and the production of CAR-T
against GPC3, and confirmed the strong cytotoxic effect on GPC3-expressing cells. Furthermore, we confirmed that it did not act on differentiated cells from iPS cells, but only on residual iPS cells. In animal experiments with mice, we elucidated that CAR-T cells administration suppressed teratoma formation when iPS cells were transplanted.

Free Research Field

循環器疾患

Academic Significance and Societal Importance of the Research Achievements

申請者はこれまでに、ヒトiPS細胞に特異的に発現し、分化心筋細胞には発現していない細胞膜表面抗原としてGPC3を同定し、これを標的抗原とするGPC3特異的細胞傷害性T細胞(CTL) 療法を開発してきた(BBRC 2019)。また、ヒトiPS細胞由来の奇形腫においてGPC3が高発現していることを初めて見出し、GPC3を標的としたCAR-T細胞療法の免疫学的アプローチにより再生医療における全ての領域で応用可能な非侵襲的腫瘍除去法の確立を可能とした。