CD47-Fc fusion proteins as putative immunotherapeutic agents for the treatment of immunological and inflammatory diseases

摘要

The human cell-surface molecule CD47 is a widely expressed transmem-brane glycoprotein that modulates the activity of neutrophils, macrophages, dendritic cells (DCs) and T cells by interacting via its extracellular domain with several endogenous ligands, including thrombospondin-1, signal regulatory protein (SIRP)-α and SIRP-β2. Homologs of CD47 also exist in certain viruses, helping them to elude host immune responses. Therefore, CD47 and its ligands appear to play important roles in the regulation of immune responses and may serve as targets for development of novel immunotherapeutic agents. Accordingly, this patent application describes soluble recom-binant CD47-Fc fusion proteins that are made up of the extracellular domain of native or mutated human CD47 or viral CD47 linked to the Fc portion of human immunoglobulin G. One example of human CD47-Fc is shown to inhibit the production of pro-inflammatory cytokines in human DCs. Moreover, a murine CD47-Fc construct is shown to alleviate inflammation in a mouse model of rheumatoid arthritis. It is thus claimed that CD47-Fc proteins may have potential for the treatment of immune and inflammatory disorders. However, further characterization of the biochemical and biological activities of these reagents will be needed to fully appraise their putative therapeutic utility.