drug_type
RELEVANT_DRUG
intervention_type
fusion protein
drug_description
CD47-blocking SIRPα–IgG4 Fc fusion protein (PF-07901801; TTI-622) that disrupts the CD47 'don't eat me' signal to promote macrophage phagocytosis.
nci_thesaurus_concept_id
C150756
nci_thesaurus_preferred_term
Maplirpacept
nci_thesaurus_definition
A soluble recombinant antibody-like fusion protein composed of the N-terminal CD47 binding domain of human signal-regulatory protein alpha (SIRPa; CD172a) linked to an Fc domain derived from human immunoglobulin G subtype 4 (IgG4), with potential immune checkpoint inhibitory, phagocytosis-inducing and antineoplastic activities. Upon administration, maplirpacept selectively targets and binds to CD47 expressed on tumor cells and blocks the interaction of CD47 with endogenous SIRPa, a cell surface protein expressed on macrophages. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of macrophage activation. This induces pro-phagocytic signaling resulting from the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1) expressed on macrophages, and results in macrophage activation and the specific phagocytosis of tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) 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 tumor cells from phagocytosis, thereby allowing these cells to proliferate and survive.
drug_category
INHIBITORY FUSION PROTEIN
drug_class
Inhibitor
drug_delivery_route
Intravenous
drug_mechanism_of_action
Soluble SIRPα–IgG4 Fc fusion that binds CD47 on tumor cells and blocks the CD47–SIRPα innate immune checkpoint, removing the 'don’t‑eat‑me' signal and activating macrophages to promote phagocytosis and antitumor clearance.
drug_name
Maplirpacept
nct_id_drug_ref
NCT05626322