Preferred Label : Anti-CD47 Monoclonal Antibody AO-176;
NCIt definition : A humanized immunoglobulin G2 (IgG2) monoclonal antibody targeting the human cell
surface antigen CD47, with potential phagocytosis-inducing and antineoplastic activities.
Upon administration, anti-CD47 monoclonal antibody AO-176 preferentially binds to
CD47 on tumor cells because it exhibits enhanced binding at the acidic pH found in
the tumor microenvironment (TME). This blocks the interaction of CD47 with signal
regulatory protein alpha (SIRPalpha), an inhibitory protein expressed on macrophages
and dendritic cells (DCs), which prevents CD47/SIRPalpha-mediated signaling and abrogates
the CD47/SIRPalpha-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, which results in macrophage activation and the specific
phagocytosis of tumor cells. Additionally, blocking CD47 signaling activates both
an anti-tumor T-lymphocyte immune response and T-cell-mediated killing of CD47-expressing
tumor cells. In addition, AO-176 induces immunogenic cell death (ICD) and releases
damage-associated molecular patterns (DAMPs) from tumor cells, thereby further stimulating
immune responses. AO-176 is also able to induce direct cytotoxic cell death by a cell
autonomous mechanism. 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 SIRPalpha, leads to the inhibition of macrophage activation and protects cancer
cells from phagocytosis, which allows cancer cells to proliferate.;
Molecule name : AO-176; AO 176;
NCI Metathesaurus CUI : CL951599;
Origin ID : C159600;
UMLS CUI : C5204561;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
