anti-SIRPa monoclonal antibody BI 770371

An 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-SIRPa monoclonal antibody BI 770371 targets and binds to SIRPa expressed on myeloid 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. BI 770371 binds to both the V1 and V2 variants of SIRPa.