The development of new antibody treatment against immune checkpoint protein PD-1 homolog

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09587
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: Harada Norihiro 順天堂大学, 医学部, 准教授 (10465065)
• Research Collaborator: AKIBA Hisaya ; ISSIKI takuma ; HARADA sonoko ; MATSUNO kei
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 免疫チェックポイント / 抗体 / PD-1H / TIM-3

Outline of Final Research Achievements

The immune system includes immune checkpoints or inhibitory pathways against excessive immune responses, as well as co-stimulatory molecules, which act to enhance immune responses. New immune checkpoints that are being evaluated in the world includes PD-1homolog (PD-1H) and T cell Ig and mucin domain (TIM)-3. In the present study, we investigated the effects of anti-PD-1H mAb and anti-TIM-3 mAb in a murine model of OVA-induced allergic airway inflammation and in a murine model of bleomycin-induced lung inflammation and fibrosis, respectively. Anti-PD-1H mAb treatment may enhance allergic airway inflammation. Moreover, anti-TIM-3 mAb treatment inhibited the phagocytic ability of alveolar macrophages, resulting in the defective clearance of apoptotic cells in lungs and enhanced bleomycin-induced lung inflammation and fibrosis, suggesting that anti-TIM-3 mAb treatment may enhance cause pneumonitis.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント分子に対する新規抗体の炎症性疾患に対する効果を解析した。がん診療に用いられている免疫チェックポイント阻害療法は、重篤な合併症として間質性肺炎を発症することが知られている。新しい免疫チェックポイント阻害薬として期待される抗TIM-3抗体も同様に、あるいは、それ以上に間質性肺炎の合併症に注意する必要がある。また、同様に抗PD-1H抗体も炎症性疾患を悪化させる可能性が考えられた。