nivolumab/relatlimab-rmbw

An injectable fixed-dose combination formulation composed of nivolumab, a human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1), and relatlimab-rmbw, a human IgG4 monoclonal antibody directed against the inhibitor receptor lymphocyte activation gene-3 (LAG-3), with immune checkpoint inhibitory and antineoplastic activities. Upon intravenous administration of nivolumab and relatlimab-rmbw, nivolumab binds to and blocks the activation of PD-1 by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This prevents PD-1-mediated signaling and PD-1-mediated inhibition of the immune response. Relatlimab binds to LAG-3 on tumor infiltrating lymphocytes (TILs) and prevents LAG-3 binding to major histocompatibility complex (MHC) class II. This prevents LAG-3-mediated signaling and LAG-3-mediated inhibition of the immune response. Together, blocking these two immune checkpoints re-activates the immune system, increases cytotoxic T lymphocytes (CTLs) proliferation and activation, and leads to a reduction in tumor growth. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity. LAG-3 expression on TILs is associated with tumor-mediated immune suppression.