CD80 Immune Checkpoint Molecule for Drug Development
Introduction to Immune Checkpoint CD80
The cluster of differentiation 80, also named CD80 and B7-1, is the type I membrane protein in the immunoglobulin superfamily. It is composed of an extracellular immunoglobulin constant-like domain and a variable-like domain for receptor binding. It is closely related to CD86 and often acts synergistically. The genes are located in the 3q13.3~q21 and 3q21 regions of human chromosomes, respectively. They have 25% amino acid homology, and the extracellular domains are both IgV+IgC.
Table.1 Immune checkpoint CD80.
Function of ligand-receptor interaction
Monocytes, activated B cells, activated T cells, macrophages, and antigen-presenting cells (APCs)
Expression of CD80
As the receptor of both CD28 and CTLA-4, CD80 can be found on the surface of various immune cells, which include monocytes, activated B cells, activated T cells, macrophages, and antigen-presenting cells (APCs). For most human malignancies, the expression of CD80 is downregulated, which results in immune surveillance evasion and the failure of immune recognition.
Function of CD80
CD80 is the receptor for both CD28 and CTLA-4 protein. In general, CD80 binds to CD28/CTLA-4 with lower affinity and fast binding kinetics. As an important costimulatory signal, this interaction results in T and B cell activation, proliferation, and differentiation. Besides, CD80 is efficient for cytotoxic T cell activation and dendritic cell licensing. Recent studies have shown that CD80 also interacts with a different ligand on Natural Killer cells, which results in cell death. The activation of the CD80 signal can increase the expression of pro-apoptotic molecules and decrease the expression of anti-apoptotic proteins, thereby inducing tumor cell apoptosis and inhibiting their growth.
Fig.1 Structure of CD80.
Preclinical and Clinical Development of Drugs Targeting CD80
Studies have shown that a variety of hematological malignancies have low or no expression of CD80 molecules. The transfer of CD80 molecules into tumor cells enhances their immunogenicity and promotes the activation of anti-tumor T cells. Clinical trials have shown that blocking CD28-CD80/CD86 signaling can sensitize chemotherapy drugs and significantly reduce tumor burden. In this case, CD80 has been served as a potential target for drug discovery against various tumors. Now, several CD80-targeting therapeutics have been discovered for tumor treatment.
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