Preferred Label : Anti-Claudin18.2/Anti-CD47 Bispecific Antibody PT886;
NCIt synonyms : Anti-CLDN18.2/Anti-CD47 Bispecific Antibody PT886; Anti-CD47/Anti-CLDN18.2 Bispecific Antibody PT886; Anti-CLDN18.2/CD47 Bispecific Antibody PT886; CLDN18.2 x CD47 Bispecific Antibody PT886;
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/anti-CD47 bispecific antibody PT886, the anti-CLDN18.2
moiety selectively targets and binds to the TAA 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 PT886 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. PT886 may also induce an anti-tumor activity through
the induction of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent
cellular phagocytosis (ADCP). 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 PT886 to CD47 on healthy hematopoietic
stem cells (HSCs) and may minimize any associated adverse effects.;
Molecule name : PT-886; PT 886;
NCI Metathesaurus CUI : CL1798778;
Origin ID : C190118;
UMLS CUI : C5783506;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
