CD154 antibody targets CD154 (CD40 ligand), a protein primarily expressed on activated T cells. CD154. a member of the tumor necrosis factor (TNF) superfamily, binds to CD40 receptors on antigen-presenting cells (e.g., B cells, dendritic cells) and non-immune cells, mediating critical immune cell interactions. This interaction is essential for T cell-dependent immune responses, including B cell activation, antibody class switching, and pro-inflammatory cytokine production.
CD154-blocking antibodies were initially explored to modulate immune hyperactivity in autoimmune diseases (e.g., systemic lupus erythematosus) or prevent transplant rejection by inhibiting CD40-CD154 signaling. Early studies in animal models showed promising immunosuppressive effects. However, clinical trials in humans faced challenges; some anti-CD154 antibodies (e.g., hu5c8) were associated with thromboembolic complications, likely due to CD154 expression on platelets.
Recent efforts focus on engineering safer CD154-targeting biologics, including non-agonistic antibodies or fragment-based designs, to minimize off-target effects. Additionally, CD154 antibodies are used experimentally to study immune regulation, particularly in models of chronic inflammation, autoimmune disorders, and cancer immunotherapy. Despite setbacks, CD154 remains a therapeutic interest, with ongoing research exploring conditional targeting, combination therapies, and localized delivery to enhance efficacy and safety.