Preferred Label : Vislarafusp Alfa;
NCIt synonyms : Anti-CD47/Anti-HER2 Bispecific Monoclonal Antibody IMM2902; Anti-CD47/HER2 Bispecific Antibody IMM2902; CD47 x HER2 Bispecific Antibody IMM2902; Anti-CD47/Anti-HER2 Bispecific Antibody IMM2902;
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 vislarafusp alfa, the anti-HER2 moiety selectively targets
and binds to the tumor-associated antigen (TAA) 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 vislarafusp alfa 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. Vislarafusp alfa may also induce an anti-tumor activity
through the induction of antibody-dependent cellular cytotoxicity (ADCC). 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, 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 vislarafusp alfa to
CD47 on healthy hematopoietic stem cells (HSCs) and may minimize any associated adverse
effects.;
UNII : GTN7CK8Y7C;
CAS number : 2850355-96-1;
Molecule name : IMM-2902; IMM 2902;
NCI Metathesaurus CUI : CL1773465;
Origin ID : C185132;
UMLS CUI : C5666949;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
