LEE, Dae Choon,ROTHSTEIN, David Mark,LEE, Young Mee
申请号：
IBIB2015/052606
公开号：
WO2015/155738A2
申请日:
2015.04.09
申请国别(地区):
WO
年份:
2015
代理人:
摘要：
The present application generally relates to the discovery that glycogen synthase kinase 3 (GSK-3) is an upstream signalling molecule that controls PD-1 transcription and Tbet expression by immune cells and in particular T-cells. Based on this discovery, and in view of the known immunosuppressive effect of PD-1 on immunity and the promoting effect of Tbet on T cell immunity, the present invention relates to the use of GSK-3 inhibitors to promote immunity, including cytotoxic T cell immunity in subjects in need thereof, especially subjects with chronic conditions wherein inhibiting PD-1 expression and/or blockade or Tbet upregulation is therapeutically desirable such as cancer and infectious conditions. Further, based on this discovery the present invention relates to the use of compounds which promote GSK-3 expression or activity to suppress immunity, especially aberrant T cell immunity in subjects in need thereof, e.g., subjects with chronic conditions wherein PD-1 upregulation or Tbet down regulation is therapeutically desirable such as allergic, autoimmune or inflammatory conditions. Also, screening methods for identifying immune agonists and antagonists, especially antibodies, are provided.La présente invention concerne dune manière générale la découverte selon laquelle la glycogène synthase kinase 3 (GSK -3) est une molécule de signalisation en amont qui commande la transcription de PD -1 et lexpression de T-Bet par des cellules immunitaires, et en particulier des lymphocytes T. Sur la base de cette découverte, et vus leffet immuno-suppresseur connu de PD -1 sur limmunité et leffet promoteur T-Bet sur limmunité due aux lymphocytes T, la présente invention concerne lutilisation dinhibiteurs de GSK -3 afin daméliorer limmunité, notamment limmunité due aux lymphocytes T cytotoxiques chez des sujets en ayant besoin, en particulier des sujets présentant des conditions chroniques dans lesquelles linhibition et/ou le blocage de lexpression de PD -1 ou la régulation à
