The 177R4 monoclonal antibody reacts with mouse Fibrinogen-like protein 1 (FGL-1). FGL-1 is a member of the fibrinogen family of proteins. Under normal physiological conditions, FGL-1 is primarily secreted from hepatocytes and contributes to mitogenic and metabolic functions. FGL-1 is produced at high levels in various tumors including lung cancer and melanoma. High FGL-1 expression is associated with resistance to anti-PD-1/PD-L1 therapy and poor prognosis of cancer patients. Recently, FGL-1 has been identified as a major inhibitory ligand for LAG-3, a receptor that negatively regulates the proliferation, activation, and effector function of T cells. In murine cancer models, the 177R4 clone has been shown to block FGL-1 binding to LAG-3 resulting in boosted T cell activity and slowed tumor growth.

InVivoMAb anti-mouse FGL-1

Wang, J., et al. (2019). “Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3.” Cell 176(1-2): 334-347 e312. PubMed

Lymphocyte-activation gene 3 (LAG-3) is an immune inhibitory receptor, with major histocompatibility complex class II (MHC-II) as a canonical ligand. However, it remains controversial whether MHC-II is solely responsible for the inhibitory function of LAG-3. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a liver-secreted protein, is a major LAG-3 functional ligand independent from MHC-II. FGL1 inhibits antigen-specific T cell activation, and ablation of FGL1 in mice promotes T cell immunity. Blockade of the FGL1-LAG-3 interaction by monoclonal antibodies stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand inter-dependent manner. FGL1 is highly produced by human cancer cells, and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. Our findings reveal an immune evasion mechanism and have implications for the design of cancer immunotherapy.