anti-SIRPalpha monoclonal antibody BYON4228

A humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting human signal-regulatory protein alpha (SIRPa; CD172a), with potential immune checkpoint inhibitory, phagocytosis-inducing and antineoplastic activities. Upon administration, anti-SIRPalpha monoclonal antibody BYON4228 targets and binds to the two allelic variants of SIRPa v1 and v2 expressed on innate immune cells, including monocytes, macrophages, dendritic cells (DCs), and neutrophils, thereby blocking the interaction between SIRPa and its ligand cluster of differentiation 47 (CD47) expressed on tumor cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis and the CD47/SIRPa-mediated suppression of the innate immune response. This induces pro-phagocytic signaling and the specific phagocytosis of tumor cells, and restores immune responses mediated by myeloid cells in the tumor microenvironment (TME). SIRPa, an innate immune checkpoint receptor expressed primarily on myeloid cells and neurons that is also known as tyrosine-protein phosphatase non-receptor type substrate 1, mediates negative regulation of phagocytosis, mast cell activation and DC activation. CD47, also known as integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSCs) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of phagocytosis and the suppression of innate immunity, which allows cancer cells to proliferate.