**Background of CD40LG Antibodies**
CD40 ligand (CD40LG), a member of the tumor necrosis factor (TNF) superfamily, is a transmembrane protein primarily expressed on activated T cells. It interacts with CD40. a receptor on B cells, dendritic cells, and other antigen-presenting cells, playing a pivotal role in adaptive immunity. This interaction triggers signaling pathways (e.g., NF-κB, MAPK) critical for B-cell activation, antibody class switching, and T-cell priming. Dysregulation of CD40-CD40LG signaling is implicated in autoimmune diseases (e.g., lupus, rheumatoid arthritis), atherosclerosis, and cancer.
CD40LG-targeting antibodies are designed to modulate this pathway. Antagonistic antibodies block CD40LG-CD40 binding, suppressing overactive immune responses in autoimmune conditions or preventing transplant rejection. Conversely, agonistic antibodies mimicking CD40LG activity enhance anti-tumor immunity by activating dendritic cells and promoting cytotoxic T-cell responses.
Early therapeutic anti-CD40LG antibodies faced challenges, including thromboembolic events linked to platelet CD40LG expression. Newer agents, such as fragment antigen-binding (Fab) variants or engineered non-Fc-binding antibodies, aim to improve safety. Clinical trials explore their efficacy in diseases like lupus, multiple sclerosis, and cancers. Research also focuses on bispecific antibodies combining CD40LG targeting with other immune checkpoints. Despite hurdles, CD40LG antibodies represent promising tools for precision immunotherapy.