Relatlimab is a type of human immunoglobulin G4 monoclonal blocking antibody. It is the world’s first Lymphocyte-Activation Gene-3 (LAG-3) inhibitor and the third immune checkpoint inhibitor with clinical application, following PD-1 and CTLA-4. Relatlimab can bind to the LAG-3 receptor which blocks the interaction between LAG-3 and its ligand to reduce LAG-3 pathway-mediated immunosuppression and promote T-cell proliferation, inducing tumor cell death. On 18 March 2022, the U.S. FDA approved the fixed-dose combination of relatlimab developed by Bristol Myers Squibb with nivolumab, under the brand name Opdualag for the treatment of unresectable or metastatic melanoma in adult and pediatric patients aged 12 and older. This study comprehensively describes the mechanism of action and clinical trials of relatlimab and a brief overview of immune checkpoint drugs currently used for the treatment of melanoma.

Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) both play important roles in diabetic nephropathy (DN). Previous studies have identified glomerular mesangial cells (GMCs) injury as a key early risk factor in the development of DN. Kaempferitrin (KM) is a potent antioxidant with hypoglycemic action. Although KM is known to protect against AGE-induced damage in GMCs, the effects and the mechanisms by which they occur are poorly understood. In this study, cultured rat GMCs were exposed to AGE-induced oxidative stress (OS) to model DN in vitro. Reactive oxygen species (ROS) was analyzed by 2′,7′-dichlorofluorescin diacetate (DCFH-DA). Superoxide dismutase (SOD) and malondialdehyde (MDA) were studied using commercial kits. Mitochondrial membrane potential (Δψm) was measured by rhodamine 123. Hoechst 33258 and annexin V and propidium iodide (PI) double staining were performed to observe the apoptosis states in GMCs, whereas apoptosis and protective mechanism in AGE-induced GMCs were investigated by Western blot. The data revealed that KM effectively increased SOD activity, decreased MDA levels, suppressed ROS generation, and protected against OS in AGE-induced GMCs. Treatment with KM also inhibited the expression of collagen IV and transforming growth factor-β1 (TGF-β1), improved mitochondrial membrane potential recovery, and suppressed the mitochondrial/cytochrome c-mediated apoptosis pathway through the expression of anti-apoptotic factors in GMCs in vitro. These findings suggest that KM may be a new potential agent in the treatment of DN in future.