Project/Area Number |
16K09883
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Kurume University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
水野 晋一 九州大学, 医学研究院, 教授 (40569430)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 造血幹細胞移植 / 組織適合抗原 / マイナー組織適合性抗原 / 遺伝子解析 / 造血幹細胞移植学 |
Outline of Final Research Achievements |
In allogeneic stem cell transplantation, the amino acid differences in proteins by SNPs (single nucleotide polymorphism) can cause immune responses, such as graft versus host disease (GVHD) and graft versus leukemia (GVL) effect. These minor histocompatibility antigens (mHAs) play an important role in eradicating leukemia cells after transplantation. However, only a small number of mHAs have been discovered and the identification of novel mHAs has been required. In this study, we developed a novel method for identification of mHAs by using next-generation sequencer. We applied whole exome sequencing for a donor and recipient, and extracted SNPs to each other. To narrow down the candidate genes of mHAs, non-synonymous SNPs are subject to be evaluated by HLA binding prediction algorithm. This study will enable us to identify novel mHAs in each pair of donor and recipient of transplantation, and will be useful for the development of an individualized immunotherapy based on mHAs.
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Academic Significance and Societal Importance of the Research Achievements |
次世代シーケンサーによる新たなマイナー組織抗原の同定は、移植片対宿主病(GVHD)や移植片対白血病効果(GVL)の予測に基づいた適切なドナー選択や、マイナー組織抗原を標的としたワクチンや養子免疫療法による個別化免疫療法につながるであろう。また、血液系腫瘍のみならず固形腫瘍においても選択的にGVT(Graft versus tumor)効果を誘導することで抗腫瘍効果を誘導し得る可能性があり、臨床への応用が期待される。
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