Preferred Label : Simridarlimab;
NCIt synonyms : Anti-CD47/PD-L1 Bispecific Antibody IBI322; Anti-CD47/Anti-PD-L1 Bispecific Antibody IBI322;
NCIt definition : A recombinant bispecific antibody targeting both the human cell surface antigen CD47
and the immunosuppressive ligand human programmed cell death-1 ligand 1 (PD-L1; cluster
of differentiation 274; CD274), with potential immunostimulating, phagocytosis-inducing
and antineoplastic activities. Upon administration, simridarlimab targets and binds
to both CD47 and PD-L1 expressed on tumor cells, with a higher binding affinity to
PD-L1 and a lower binding affinity to CD47. The CD47 binding by simridarlimab 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), specifically
expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related
protein (LRP), expressed on macrophages, and results in macrophage activation and
the specific phagocytosis of CD47-expressing tumor cells. The binding of simridarlimab
to PD-L1 blocks its binding to and activation of its receptor programmed cell death
1 (PD-1; cluster of differentiation 279; CD279). This reverses T-cell inactivation
caused by PD-1/PD-L1 signaling and enhances the cytotoxic T-lymphocyte (CTL)-mediated
anti-tumor immune response against PD-L1-expressing tumor cells. CD47, also called
integrin-associated protein (IAP), is a tumor-associated antigen (TAA), widely expressed
on normal, healthy cells, such as red blood cells 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. By co-targeting
CD47 and PD-L1 with a higher binding affinity to PD-L1, simridarlimab may more selectively
bind to tumor cells expressing both CD47 and PD-L1, reducing the side effects caused
by the blockade of CD47 expressed on healthy hematopoietic stem cells (HSCs). PD-L1
is overexpressed by many human cancer cell types. PD-L1 binding to PD-1 on T-cells
suppresses the immune system and results in immune evasion. PD-1, a transmembrane
protein belonging to the immunoglobulin superfamily (IgSF) expressed on activated
T-cells, is a negative regulator of the immune system that limits the expansion and
survival of CD8-positive T-cells.;
UNII : 0VN2H61ATB;
CAS number : 2378862-90-7;
Molecule name : IBI-322; IBI 322;
NCI Metathesaurus CUI : CL1642583;
Origin ID : C176744;
UMLS CUI : C5706692;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
