Preferred Label : Anti-CLDN18.2/CD47 Bispecific Antibody AK132;
NCIt synonyms : CD47 x CLDN18.2 Bispecific Antibody AK132; Anti-Claudin18.2/CD47 Bispecific Antibody AK132; Anti-CLDN18.2/Anti-CD47 Bispecific Antibody AK132; Anti-CD47/Anti-CLDN18.2 Bispecific Antibody AK132; CLDN18.2 x CD47 Bispecific Antibody AK132;
NCIt definition : A bispecific antibody directed against both the tumor-associated antigen (TAA) Claudin18.2
(CLDN18.2; A2 isoform of claudin-18) and the human cell surface antigen CD47, with
potential immunostimulating, phagocytosis-inducing and antineoplastic activities.
Upon administration of anti-CLDN18.2/CD47 bispecific antibody AK132, the anti-CLDN18.2
moiety selectively targets and binds to CLDN18.2 on CLDN18.2-expressing tumor cells,
thereby improving the binding of the anti-CD47 moiety to the CLDN18.2-expressing tumor
cells. The CD47 binding by AK132 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 the CLDN18.2-expressing tumor cells. Additionally, blocking CD47 signaling activates
an anti-tumor T-lymphocyte immune response and T-cell-mediated killing of CLDN18.2-expressing
tumor cells. CD47, also called integrin-associated protein (IAP), is widely expressed
on normal, healthy cells, such as red blood cells (RBCs) and platelets, 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. CLDN18.2, a tight
junction protein and stomach-specific isoform of Claudin-18, is expressed on a variety
of tumor cells. Its expression in healthy tissues is strictly confined to short-lived
differentiated epithelial cells of the gastric mucosa. Co-targeting CD47 and CLDN18.2
may limit the binding of AK132 to CD47 on healthy hematopoietic stem cells (HSCs)
and may minimize any associated adverse effects.;
Molecule name : AK 132; AK-132;
NCI Metathesaurus CUI : CL1927042;
Origin ID : C204802;
UMLS CUI : C5908059;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
