Regulation of anti-tumor immune response by cell-surface engineering and development of innovative proliferation method of tumor infiltrating T cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22951
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: National Institute of Advanced Industrial Science and Technology (2020-2021); The University of Tokyo (2019)
• Principal Investigator: Teramura Yuji 国立研究開発法人産業技術総合研究所, 生命工学領域, 上級主任研究員 (10365421)
• Co-Investigator(Kenkyū-buntansha): 垣見 和宏 東京大学, 医学部附属病院, 特任教授 (80273358)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 細胞表面工学 / 免疫療法 / CD8陽性T細胞 / PEG脂質

Outline of Final Research Achievements

There is a promising cancer immunotherapy in which tumor-infiltrating T cells in the tumor tissue of cancer patients are proliferated in vitro and then infused again into the patient. However, although it is possible to culture tumor-infiltrating T cells efficiently in malignant melanoma, it is difficult to culture them in solid cancer, and it is known that it is very difficult to cultivate and proliferate due to the immunosuppressive environment in the tumor. In this study, we apply cell surface engineering technique using polyethylene glycol-conjugated lipids to immunoregulatory technology to modulate the surface of cancer cells and control immunosuppressive signals in cancer cell-T cell interactions. Here, the purpose was to introduce CD80 into tumor cells to efficiently proliferate tumor-specific T cells.

Free Research Field

バイオマテリアル工学

Academic Significance and Societal Importance of the Research Achievements

近年、PD-1/PD-L1経路を阻害する免疫チェックポイント阻害剤が臨床応用され、大きな成果を上げている。抗PD-1抗体/抗PD-L1抗体の経験から、免疫抑制の解除には、このPD-1/PD-L1経路の阻害だけでは不十分であり、CD80/CD86からT細胞上のCD28分子へのシグナル伝達が必要であることが明らかになった。本研究が成功すれば、これまで困難であった固形癌への免疫療法の開発に繋がり、多くのがん患者を救うことが可能になるものと期待している。