Preferred Label : SIRPa-4-1BBL Fusion Protein DSP107;
NCIt synonyms : CD172a-4-1BBL Trimeric Fusion Protein DSP107; SIRPa-4-1BBL Dual Signaling Protein DSP107; SIRPa-4-1BBL DSP107;
NCIt definition : A bi-functional, trimeric, fusion protein consisting of the extracellular domains
(ECDs) of human signal-regulatory protein alpha (SIRPalpha; SIRPa; CD172a) fused to
a 4-1BB ligand (4-1BBL), with potential immune checkpoint inhibitory, immunostimulating
and antineoplastic activities. Upon administration, the SIRPa-4-1BBL fusion protein
DSP107 selectively targets and binds to both CD47 expressed on tumor cells and 4-1BB
(CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) expressed on
T-cells and natural killer (NK) cells. Binding to CD47 blocks the interaction of CD47
with endogenous SIRPa, a cell surface protein expressed on macrophages. This prevents
CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of
macrophage activation and phagocytosis of cancer cells. 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-1
(LRP-1), which is expressed on macrophages, and results in macrophage activation and
the specific phagocytosis of tumor cells. The binding of 4-1BBL to 4-1BB activates
4-1BB-mediated signaling, induces cytotoxic T-lymphocyte (CTL) proliferation, cytokine
production and promotes a CTL-mediated anti-tumor immune response as well as NK-mediated
tumor cell killing. The crosslinking specifically enables the activation of 4-1BB-mediated
signaling in T-cells and NK cells in the tumor microenvironment (TME), allowing targeted
immune responses in the TME. 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 cancer cells from phagocytosis, thereby allowing cancer cells to proliferate.
4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is
an inducible costimulatory receptor that plays a key role in T-cell proliferation,
survival and cytolytic activity.;
Molecule name : DSP 107; DSP-107;
NCI Metathesaurus CUI : CL1407805;
Origin ID : C174171;
UMLS CUI : C5418071;
Semantic type(s)
- concept_is_in_subset
- has_target
