Preferred Label : Anti-CLDN18.2/CD47 Bispecific Antibody SG1906;
NCIt synonyms : Anti-CLDN18.2/Anti-CD47 Bispecific Antibody SG1906; Anti-CD47/Anti-CLDN18.2 Bispecific Antibody SG1906; Anti-Claudin18.2/CD47 Bispecific Antibody SG1906; CLDN18.2 x CD47 Bispecific Antibody SG1906;
NCIt definition : A recombinant, immunoglobulin G1 (IgG1) 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 SG1906, 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 SG1906 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 SG1906 to
CD47 on healthy hematopoietic stem cells (HSCs) and may minimize any associated adverse
effects.;
Molecule name : SG 1906; SG-1906;
NCI Metathesaurus CUI : CL1915065;
Origin ID : C200799;
UMLS CUI : C5854585;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
