Preferred Label : Spevatamig;
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; Anti-Claudin18.2/Anti-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 spevatamig, 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 spevatamig 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. Spevatamig 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 spevatamig to CD47 on healthy hematopoietic
stem cells (HSCs) and may minimize any associated adverse effects.;
UNII : LVB74L4PM2;
CAS number : 2928515-36-8;
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
