Anti-SIRPa Monoclonal Antibody BSI-082

**Semantic type:** Amino Acid, Peptide, or Protein|Immunologic Factor|Pharmacologic Substance

**Definition:** A human immunoglobulin G1 kappa (IgG1k) monoclonal antibody directed against human signal-regulatory protein alpha (SIRPa; CD172a), including variants SIRPaV1, SIRPaV2 and SIRPaV8, with potential immune checkpoint inhibitory, phagocytosis-inducing and antineoplastic activities. Upon administration, anti-SIRPa monoclonal antibody BSI-082 targets and binds to SIRPa, a cell surface protein expressed on macrophages, thereby blocking the interaction between SIRPa and cluster of differentiation 47 (CD47) expressed on tumor cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages, and results in macrophage activation and the specific phagocytosis of tumor cells. SIRPa, also known as tyrosine-protein phosphatase non-receptor type substrate 1, mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. SIRPaV1, SIRPaV2 and SIRPaV8 are the main SIRPa variants in human. CD47, also called 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 macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate. The engineered Fc domain of BSI-082 prevents Fc gamma receptor (FcgR) binding, which decreases antibody-dependent cellular cytotoxicity (ADCC), and promotes neonatal Fc receptor (FcRn) binding, which increases the half-life of BSI-082.

**Synonyms:** - Anti-SIRPa Variant V1/V2/V8 Monoclonal Antibody BSI-082 - Anti-SIRPaV1/SIRPaV2/SIRPaV8 Monoclonal Antibody BSI-082 - Anti-SIRPalpha Monoclonal Antibody BSI-082 - BSI 082 - BSI-082 - BSI082