The study of control of immortalization of EBV-infected cells and the development of the immortalization inhibitor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08336
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Imadome Ken-Ichi 国立研究開発法人国立成育医療研究センター, 高度感染症診断部, 部長 (70392488)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: CD40シグナル / EBウイルス / PTLD

Outline of Final Research Achievements

We used humanized mice in this study and aimed at the elucidation of the control of immortalization (transformation) of EBV-infected cells, and at the development of the immortalization inhibitor. And we aimed at the establishment of the PTLD prophylaxis.
We converted human cells from insect cells to manufacture CD40Ig of the CD40-signal inhibitor. CD40 signal was inhibited by CD40Ig which reduced the efficiency of immortalization. We enabled increase of the inhibition efficiency and the weight loss of the dose. Also, we paid attention to CD40 ligand (CD40L), and manufacture of CD40LIg which the signal inhibition to CD40L.As a result, manufacture of secretor CD40Ig and secretor CD40LIg using human cells and a collection were successful.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

Epstein-Barr virus (EBウイルス：EBV)は移植医療後のリンパ増殖症 (PTLD: Posttransplant lymphoprolifirative disorder)を引き起こす代表的なウイルスである。PTLDは、小児の臓器移植後に発生する悪性腫瘍の90% 以上を占め、移植医療成績を左右する重要な合併症である。PTLD発症は成人よりも10倍以上小児が多く、その予防と治療法の確立は急務である。本研究の成果の実用化により、EBV未感染移植治療実施小児に対し、CD40Ig,CD40LIgを用いることでPTLD発症予防が可能になる初めての治療薬となることが考えられる。