MEK inhibitors selectively suppress GVHD while sparing antitumor and antiviral immunity after allogeneic hematopoietic stem cell transplantation

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461451
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University (2016); Saga University (2014-2015)
• Principal Investigator: Shindo Takero 京都大学, 医学研究科, 助教 (10646706)
• Co-Investigator(Renkei-kenkyūsha): OKADA Seiji 熊本大学, 医学研究科, 教授 (50282455) ; KUBOTA Yasushi 佐賀大学, 医学部, 講師 (60570413) ; TAWARA Isao 三重大学, 医学部, 助教 (80378380)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 造血幹細胞移植 / 移植片対宿主病 / 抗腫瘍免疫 / 抗ウイルス免疫 / MEK阻害剤 / 免疫抑制剤

Outline of Final Research Achievements

We investigated the roles of MEK inhibitors in regulation of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects after allogeneic hematopoietic stem cell transplantation. We confirmed that a MEK inhibitor trametinib suppresses GVHD while sparing GVT effects in several different murine bone marrow transplant models. Meanwhile, the calcineurin inhibitor tacrolimus abrogated GVT effects, which confirmed the priority of trametinib. These results were published as a research article in JCI Insight in 2016 July, and were widely broadcasted. Currently, we are concentrating to design and start a clinical trial in humans with trametinib.

Free Research Field

血液内科学