LAG-3 = LYMPHOCYTE ACTIVATION GENE-3

Incyte is developing an antagonistic anti-LAG-3 antibody.

Lymphocyte activation gene-3 (LAG-3) is a co-inhibitory receptor upregulated on the surfaces of activated CD4+ and CD8+ T cells and other lymphocytes. LAG-3 binds to MHC Class II on antigen-presenting cells with greater affinity than CD4. Signaling through LAG-3 inhibits proliferation and cytokine production in activated effector T cells (T-effs).

In cancer, tumor infiltrating T-effs that become exhausted and dysfunctional through chronic antigenic stimulation may co-express LAG-3 and PD-1. Combined inhibition of the LAG-3 and PD-1 pathways can improve anti-tumor responses by exhausted T-effs in a synergistic manner.

LAG-3 expression on regulatory T cells (T-regs) may also be associated with enhanced T-reg function.

The therapeutic blockade of LAG-3 may strengthen anti-tumor immune responses by restoring activity in exhausted T-effs and inhibiting T-regs.