SP0017 Modulation of CD27-CD70 Interactions

After binding its natural ligand CD70, CD27, a tumor necrosis factor receptor (TNFR)-associated factor-binding member of the TNFR family, regulates cellular activity in subsets of T, B, and natural killer cells as well as hematopoietic progenitor cells. In normal immune responses, CD27 signaling is limited predominantly by the restricted expression of CD70, which is only transiently expressed by cells of the immune system upon activation. Studies performed in CD27-deficient and CD70-transgenic mice have defined a non-redundant role of this receptor-ligand pair in shaping adaptive T-cell responses. Moreover, adjuvant properties of agonistic CD27 monoclonal antibodies have been exploited for the design of anti-cancer vaccines. However, continuous CD27-CD70 interactions may cause immune dysregulation and immunopathology in conditions of chronic immune activation such as during persistent virus infection and autoimmune disease. The latter observations provide a rational for modulating CD27-CD70 interactions in immune mediated inflammatory diseases. For a review see Nolte, MA et al., Immunol Rev. 2009, 229:216-31. Disclosure of Interest None declared