Preferred Label : Antibody receptor-Trap Fusion Protein IMM2520;
NCIt synonyms : Monoclonal Antibody-receptor Recombinant Protein IMM2520; mAb-Trap IMM2520; Bispecific Monoclonal Antibody-Trap Fusion Protein IMM2520; Bispecific mAb-Trap Fusion Protein IMM2520; CD47xPD-L1 Bispecific Molecule IMM2520;
NCIt definition : An immunoglobulin G1 (IgG1) Fc-containing bispecific antibody-receptor fusion protein
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 immune checkpoint inhibitory, immunostimulating, phagocytosis-inducing
and antineoplastic activities. Upon administration, the antibody receptor-Trap fusion
protein IMM2520 targets and binds to both CD47 and PD-L1 expressed on tumor cells.
The CD47 binding by IMM2520 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 IMM2520 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. In addition, IMM2520 induces Fc-mediated antibody-dependent cell-mediated
cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). 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, IMM2520 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 : IMM 2520; IMM-2520;
NCI Metathesaurus CUI : CL1907456;
Origin ID : C200454;
UMLS CUI : C5854534;
Semantic type(s)
- concept_is_in_subset
- has_target
