Preferred Label : Anti-PD-L1/Anti-CD47 Bispecific Monoclonal Antibody LB101;
NCIt synonyms : Anti-PDL1/CD47 Bispecific Monoclonal Antibody LB101; PD-L1xCD47 LockBody Bispecific Monoclonal Antibody LB101; PD-L1 x CD47 Bispecific Antibody LB101; Anti-CD47/Anti-PD-L1 Bispecific Antibody LB101; Anti-PD-L1/Anti-CD47 Bispecific Antibody LB101; Anti-PD-L1/CD47 Bispecific Antibody LB101;
NCIt definition : A conditionally-activatable tetravalent 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. LB101 contains two anti-CD47
domains blocked by two anti-PD-L1 domains, with human immunoglobulin (Ig) G-derived
hinges linking the anti-CD47 and anti-PD-L1 domains. Upon administration of anti-PD-L1/anti-CD47
bispecific monoclonal antibody LB101, the PD-L1 targeting domains target and bind
to PD-L1 expressed on tumor cells. The IgG-derived hinges are naturally degraded in
the tumor microenvironment (TME) and, upon cleavage, unblock the CD47 domains. The
CD47 domains target and bind to CD47, thereby blocking 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 induces
antibody-dependent cellular phagocytosis (ADCP). The binding of LB101 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, which protects cancer cells from
phagocytosis and allows cancer cells to proliferate. 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. By co-targeting
CD47 and PD-L1 and activating the CD47 domains within the TME, LB101 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).;
Molecule name : LB 101; LB-101;
NCI Metathesaurus CUI : CL1907541;
Origin ID : C200549;
UMLS CUI : C5854558;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
