Preferred Label : Timdarpacept;
NCIt synonyms : SIRP-alpha Fc Fusion Protein IMM01; SIRPa-IgG1-Fc Fusion Protein IMM01; SIRPa-Fc Fusion Protein IMM01;
NCIt definition : A recombinant fusion protein composed of human signal-regulatory protein alpha (SIRP-alpha;
SIRPa; CD172a) linked to an Fc domain derived from human immunoglobulin G1 (IgG1),
with potential immune checkpoint inhibitory, phagocytosis-inducing and antineoplastic
activities. Upon administration, timdarpacept selectively targets and binds to CD47
expressed on tumor cells and blocks the interaction of CD47 with endogenous SIRPa,
an inhibitory protein expressed on macrophages and dendritic cells (DCs), thereby
preventing CD47/SIRPa-mediated signaling. This abrogates the CD47/SIRPa-mediated inhibition
of macrophage activation, and 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), which is expressed on macrophages.
This results in macrophage activation and the specific phagocytosis of tumor cells.
Additionally, blocking CD47/SIRPa signaling activates an anti-tumor T-lymphocyte immune
response and T-cell-mediated killing of tumor cells. CD47, also called integrin-associated
protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic
stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression
of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation
and protects tumor cells from phagocytosis, thereby allowing these cells to proliferate
and survive.;
UNII : 664WQ5KSP8;
CAS number : 2749520-17-8;
Molecule name : IMM 01; IMM-01;
NCI Metathesaurus CUI : CL1906070;
Origin ID : C199120;
UMLS CUI : C5855384;
Semantic type(s)
- concept_is_in_subset
- has_target
