cytokine storm, page-2

LAG-3 as a negative regulator of T cells

On T cells, LAG-3 is a co-inhibitory receptor physically associated with the T cell receptor and expressed on activated T cells and consequently, if LAG-3 is expressed on T cells, it has an inhibitory effect on activated T cells.

When LAG-3 expressed on an activated CD8+ T cell binds to MHC class II at the same time as the T cell receptor (TCR) is binding to MHC class I on an APC, the LAG-3 binding stops calcium signaling which leads to a reduction in cytokine production and a decline in immune response.

Such a negative feedback mechanism is necessary to actively switch off an immune response when it is no longer required. In this way it negatively regulates cellular proliferation, activation, and homeostasis of T cells, in a similar fashion to CTLA-4 and PD-1 and has been reported to play a role in Treg suppressive function. This mechanism plays a role for cancer and autoimmune diseases.

Based on these two different mechanisms of action, Immutep has developed four product candidates that are currently being developed at Immutep or have been out-licensed to one of our pharmaceutical partners for development and commercialization.