CD40:CD40L TR-FRET Assay Kit

CD40 (cluster of differentiation 40), also known as TNFRSF5 ((tumor necrosis factor)-receptor superfamily 5) is a type I transmembrane protein involved in the activation of antigen presenting cells (APCs), such as dendritic cells, B cells and macrophages. It can also be found in epithelial and endothelial cells, and tumor cells. CD40L (CD40 ligand), also known as TNFSF5 and CD154, is a type II membrane glycoprotein that exists in cells in membrane bound (mCD40L) and soluble (sCD40L) forms. It is found at high levels in activated CD4+ T cells, and at lower levels in Th1, Th2, Th17 and Tregs. Expression can also be induced in NK cells, CD8+ T cells, basophils, and others. CD40 and CD40L are stimulatory immune checkpoints, and their signaling is mediated by different TRAF (TNF receptor associated factor), in a cell and stimuli dependent mode. For example, it mediates the activation of the NF-κB (nuclear factor kappa-B) pathway. CD40 is implicated in Hyper Ig-M immunodeficiency, where IgM is found at high levels in the serum, while other IgG are present at lower-than-normal levels, and patients have higher risk of developing autoimmune diseases and cancer. The role of CD40 and CD40L as immune checkpoints makes them highly attractive targets in cancer therapy, and several clinical trials using anti-CD40 or anti-CD40L agonist antibodies or increasing their expression are underway targeting both hematological and solid tumors. The inhibition of CD40:CD40L interaction is also clinically relevant, and clinical trials have been focusing on treatment options for lupus, rheumatoid arthritis and ALS (amyotrophic lateral sclerosis). Further studies and development of refined therapies will continue to benefit the cancer therapy field and patients suffering from autoimmune disorders.