Development of next-generation immunosuppressive therapy in organ transplantation using anti-CD70 antibody

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Osaka University
• Principal Investigator: Ichimaru Naotsugu 大阪大学, 医学系研究科, 寄附講座准教授 (70346211)
• Co-Investigator(Kenkyū-buntansha): 梨井 康 国立研究開発法人国立成育医療研究センター, 移植免疫研究室, 室長 (60321890) ; 高原 史郎 大阪大学, 医学系研究科, 招へい教授 (70179547) ; 貝森 淳哉 大阪大学, 医学系研究科, 寄附講座准教授 (70527697)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗CD70抗体 / 免疫抑制療法 / 臓器移植

Outline of Final Research Achievements

Anti-CD70 antibody treatment induced permanent acceptance (>100 days) of allogeneic cardiac grafts in mice, while median cardiac graft survival of no treatment group was 8 days after transplant surgery. Anti-CD70 antibody treatment induced regulatory dendritic cells in spleen and graft. The splenocytes from anti-CD70 antibody treated C3H recipients bearing B6 grafts were adoptively transferred into naive C3H mice, and then the C3H mice were given B6 or Balb/c allografts. Histologic studies of harvested cardiac grafts revealed few mononuclear cell infiltration in B6 allografts, which suggested donor specific tolerance. The regulatory dendritic cells generated following anti-CD70 antibody treatment were actively immunosuppressive. These results showed that anti-CD70 antibody treatment induced regulatory dendritic cells in recipient mice and effectively prevented rejection in cardiac transplantation model.

Free Research Field

臓器移植

Academic Significance and Societal Importance of the Research Achievements

末期臓器不全患者において，臓器移植は唯一の根治療法となる。ヒトでの同種臓器移植においては拒絶反応を防ぐために数種の免疫抑制薬の併用が欠かせない。残念ながらそれでも拒絶反応は完全には防ぎえないだけでなく，本来宿主に有用な腫瘍免疫などを抑制してしまい悪性腫瘍の頻度が増加するという重大な副作用を生じている。
本研究成果により，移植臓器に対してだけ免疫反応を抑制し，抗腫瘍免疫などの宿主に有用な免疫反応を維持するドナー特異的免疫寛容に抗CD70抗体が有用である可能性が示唆され，その機序は制御性樹状細胞の誘導によることが示された。