Identification of novel immunecheckpoints and development of methods to inhibit them

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Yamanashi
• Principal Investigator: Inozume Takashi 山梨大学, 大学院総合研究部, 講師 (80334853)
• Research Collaborator: YAGUCHI tomonori ; Togashi Yosuke
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗PD-1抗体 / 抗CTLA-4抗体 / TIGIT / LAG3 / メラノーマ / 免疫チェックポイント阻害剤

Outline of Final Research Achievements

In this study we have shown (1) and (2) as below, in the in vitro experiment using human melanoma tumor infiltrating lymphocytes that are thought to play central role in tumor rejection, and, in the in vivo tumor-treatment model using a humanizes mouse model.
(1) PD-1, TIGIT, and LAG3 are selectively expressed by tumor-infiltrating, tumor-specific T cells, and cooperatively suppress T cell function (2) Co-blockade for their signals by the blocking antibodies synergistically activate the tumor specific T cells.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

現在、がん治療に使用される抗PD-1抗体、抗CTLA-4抗体は一部のメラノーマ患者に高い効果を示すが、効果がない例、強い副作用が出る例も存在する。本研究では新規免疫チェックポイント候補であるTIGITとLAG3をPD-1とともに阻害すれば効果増強、副作用軽減が可能となる可能性を示した。この結果は今後の免疫チェックポイント阻害剤によるがん治療の効率化、安全化に高く貢献する可能性がある。