Development of novel immunotherapy for chronic inflammatory diseases

• Project/Area Number: 18H02730
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Osaka University
• Principal Investigator: Nakagami Hironori 大阪大学, 医学系研究科, 寄附講座教授 (20325369)
• Co-Investigator(Kenkyū-buntansha): 樂木 宏実 大阪大学, 医学系研究科, 教授 (20252679) ; 島村 宗尚 大阪大学, 医学系研究科, 寄附講座准教授 (60422317)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: ワクチン / 抗体 / 慢性炎症 / アラーミン / 老化細胞

Outline of Final Research Achievements

S100A9 (S100 calcium-binding protein A9) is known as an inflammatory trigger factor through TLR and RAGE, called as alarmin. It also contribute the thrombosis formation through Cd36 signaling in platelet, which was released from an activation platelet at acute vascular injury. Thus, we evaluated the effect of S100A9 vaccine in a mouse Fe-induced vascular injury model in mouse carotid artery.
Senescence cells secrets the inflammatory factors to affect the tissue aging, and the removal of senescence cells might be novel therapy to achieve the life expand as well as improvement of aging related diseases. We focused on Senescent T cells which was defined as CD4+CD44hiCD62LoPD-1+CD153+ and developed CD153 vaccine. After being fed a HFD for 10-11 weeks, adipose senescent T cell accumulation was significantly reduced in the adipose tissue of CD153- vaccinated mice, accompanied by glucose tolerance and insulin resistance.

Academic Significance and Societal Importance of the Research Achievements

我々はこれまで液性免疫主導の抗体誘導ワクチンの開発に取り組んできた。これは内因性分子に対する免疫応答を惹起して抗体産生を誘導する手法であり、生体内で疾患発症に先立ち上昇するアラーミンあるいは老化細胞を標的とした新規免疫治療法を確立し、早期治療介入による脳梗塞・心筋梗塞の予防、健康寿命の延伸を目指した治療を提案する。

Research Products

• [Journal Article] The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice (2020)
  • Author(s): Yoshida S, Nakagami H, Hayashi H, Ikeda Y, Sun J, Tenma A, Tomioka H, Kawano T, Shimamura M, Morishita R, Rakugi H.
  • Journal Title: Nat Commun Volume: 11(1) Issue: 1 Pages: 2482-2482
  • DOI: 10.1038/s41467-020-16347-w
  • Peer Reviewed / Open Access
• [Journal Article] Cellular senescence and senescence-associated T cells as a potential therapeutic target. (2020)
  • Author(s): Nakagami H
  • Journal Title: Geriatr Gerontol Int. Volume: 20(2) Issue: 2 Pages: 97-100
  • DOI: 10.1111/ggi.13851
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic Vaccine Against S100A9 (S100 Calcium-Binding Protein A9) Inhibits Thrombosis Without Increasing the Risk of Bleeding in Ischemic Stroke in Mice (2018)
  • Author(s): Kawano T, Shimamura M, Nakagami H, Iso T, Koriyama H, Takeda S, Baba K, Sasaki T, Sakaguchi M, Morishita R, Mochizuki H.
  • Journal Title: Hypertension Volume: 72(6) Issue: 6 Pages: 1355-1364
  • DOI: 10.1161/hypertensionaha.118.11316
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Development of therapeutic vaccine for chronic diseases (2020)
  • Author(s): Hironori Nakagami
  • Organizer: Korean Society for Molecular and Cellular Biology
  • Int'l Joint Research / Invited