CD223. also known as LAG-3 (Lymphocyte Activation Gene-3), is a cell surface protein predominantly expressed on activated T cells and regulatory T cells (Tregs). It functions as an immune checkpoint molecule that negatively regulates T-cell activation and effector functions to prevent excessive immune responses. Structurally homologous to CD4. LAG-3 binds to MHC class II molecules with higher affinity, modulating antigen-presenting cell (APC) interactions and T-cell receptor signaling. Dysregulation of LAG-3 is implicated in immune evasion in cancers and chronic infections. CD223 antibodies are designed to block LAG-3’s inhibitory activity, thereby restoring T-cell proliferation and cytotoxicity. Preclinical studies highlight their potential in enhancing antitumor immunity, particularly when combined with PD-1/PD-L1 inhibitors. In 2022. the FDA approved relatlimab, a LAG-3-blocking antibody, in combination with nivolumab (anti-PD-1) for advanced melanoma, marking a milestone in dual checkpoint inhibition. Ongoing research explores CD223 antibodies in other malignancies and autoimmune diseases, aiming to optimize therapeutic efficacy while managing immune-related adverse events. These antibodies represent a promising avenue for overcoming resistance to existing immunotherapies.