Preferred Label : Anti-CD47/Anti-HER2 Bispecific Antibody D3L-001;
NCIt synonyms : CD47 x HER2 Bispecific Antibody D3L-001; Anti-HER2/CD47 Bispecific Antibody D3L-001; Anti-CD47/HER2 Bispecific Antibody D3L-001; Anti-HER2/Ant-CDi47 Bispecific Antibody D3L-001; Anti-CD47/Anti-HER2 Bispecific Monoclonal Antibody D3L-001;
NCIt definition : A bispecific antibody directed against both the human tyrosine kinase receptor epidermal
growth factor receptor 2 (HER2; ErbB2; HER-2) and the human cell surface antigen CD47,
with potential immunostimulating, phagocytosis-inducing and antineoplastic activities.
Upon administration of anti-CD47/anti-HER2 bispecific antibody D3L-001, the anti-HER2
moiety selectively targets and binds to HER2 on HER2-expressing tumor cells, thereby
improving the binding of the anti-CD47 moiety to the HER2-expressing tumor cells.
The CD47 binding by D3L-001 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), which is specifically expressed on the surface of tumor
cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed
on macrophages, which results in macrophage activation and the specific phagocytosis
of the HER2-expressing tumor cells. Additionally, blocking CD47 signaling activates
an anti-tumor T-lymphocyte immune response and T-cell-mediated killing of HER2-expressing
tumor cells. CD47, also called integrin-associated protein (IAP), is 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. HER-2, a tumor-associated
antigen (TAA) overexpressed on a variety of tumor cell types, plays an important role
in tumor cell proliferation, differentiation and survival. Co-targeting CD47 and HER2
may limit the binding of D3L-001 to CD47 on healthy hematopoietic stem cells (HSCs)
and may minimize any associated adverse effects.;
Molecule name : D3L 001; D3L-001;
NCI Metathesaurus CUI : CL1926406;
Origin ID : C204137;
UMLS CUI : C5908030;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
