PD-L1/CD47 Antibodies

Target Information

Programmed death receptor ligand 1 (PD-L1, also called B7-H1) is a recently described B7 family member. To date, one specific receptor has been identified that can be ligated by PD-L1. This receptor, programmed death receptor 1 (PD-1), has been shown to negatively regulate T-cell receptor (TCR) signaling. Upon ligating its receptor, PD-L1 has been reported to decrease TCR-mediated proliferation and cytokine production. PD-L1 expression was found to be abundant on many murine and human cancers and could be further up-regulated upon IFN-gamma stimulation. Thus, PD-L1 might play an important role in tumor immune evasion.

CD47, known as integrin-associated protein (IAP), is a glycosylated transmembrane glycoprotein with five domains, expressed widely across hematopoietic cells like T and B cells, monocytes, platelets, and erythrocytes, as well as non-hematopoietic cells. It interacts with integrins such as CD51/CD61 and CD41/CD61, and serves as a receptor for thrombospondin, mediating bi-directional signaling that affects neural synaptic activity and macrophage phagocytosis. CD47 acts as a ligand for CD172a (SIRP alpha), an inhibitory receptor on macrophages, preventing phagocytosis of CD47-positive cells. This interaction influences cell migration, B cell adhesion, T cell activation, and neuronal development, particularly in synapse-rich brain and retina regions. It also modulates chondrocyte responses to mechanical signals. T cell expression of CD47 can lead to activation or apoptosis in the presence of thrombospondin. Monoclonal antibody stimulation of CD47 has been shown to induce CD4+CD25- suppressive activity and increase Foxp3 expression. CD47's role in membrane transport, signal transduction, and its broad tissue distribution highlight its significance in various physiological processes.