Lymphocyte-activation gene 3 (LAG-3) (LAG-3)

Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a cell surface receptor belonging to the immunoglobulin superfamily, primarily expressed on activated T cells, natural killer (NK) cells, and plasmacytoid dendritic cells (UniProt P18627). It serves as a critical immune checkpoint by binding to major histocompatibility complex (MHC) class II molecules with higher affinity than CD4, thereby delivering inhibitory signals that suppress T-cell activation, proliferation, and cytokine production (PubMed: 15034570). In the context of oncology, persistent antigen exposure in the tumor microenvironment leads to the upregulation of LAG-3, which contributes to T-cell exhaustion and allows tumors to evade immune surveillance (PubMed: 28434868). Therapeutic strategies, such as the monoclonal antibody fianlimab (REGN3767), target LAG-3 to block its inhibitory interactions and restore the anti-tumor activity of effector T cells. Clinical evidence suggests that LAG-3 inhibition is particularly effective when combined with PD-1/PD-L1 blockade, offering a synergistic approach to overcoming resistance in various malignancies, including melanoma and lung cancer (Regeneron Pharmaceuticals, 2023).

Other names

CD223Lymphocyte-activation gene 3 proteinLAG3

LAG-3 antagonist; blocks the binding of LAG-3 to MHC class II and other ligands (e.g., FGL1) to prevent inhibitory signaling in T-cells and enhance anti-tumor immunity (PubMed: 30309865).