Relatlimab

Lymphocyte-activation gene 3 (LAG-3) - also known as CD223 - is a type I transmembrane protein belonging to the immunoglobulin superfamily. Its expression on activated T-cells is induced following antigen stimulation, and they serve a number of functions including the inhibition of Th1 cell proliferation and the reduction of cytokine production - such as IL-2, IFNγ, and TNF - in these activated T-cells. Ligands of LAG-3 include antigen-presenting cells such as MHC class II molecules and liver sinusoidal endothelial cell lectin (LSECtin), the latter of which has been shown to promote tumor progression when expressed on melanoma cells by inhibiting anti-tumor T-cell responses.

As LAG-3 expression is tied to antigen presentation, continuous antigen exposure owing to chronic infection or tumor-associated antigens can lead to high and sustained expression of LAG-3 on T-cells, which eventually lose their effector functions by becoming functionally "exhausted". This loss of T-cell function leads to lessened immunosurveillance and promotes tumor escape.

Relatlimab is a human IgG4 monoclonal antibody that binds LAG-3 and inhibits its signaling pathway, the antagonism of which promotes T-cell proliferation, cytokine secretion, and, subsequently, restored tumor immunosurveillance. Used in combination with nivolumab, a PD-1 receptor blocker, relatlimab has been shown to potentiate the anti-tumor effects of PD-1 blockade.