Preferred Label : Anti-CD47/Anti-HER2 Bispecific Antibody IMM2902;
NCIt synonyms : Anti-CD47/Anti-HER2 Bispecific Monoclonal Antibody IMM2902; Anti-CD47/HER2 Bispecific Antibody IMM2902; CD47 x 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 anti-CD47/anti-HER2 bispecific antibody IMM2902, 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 IMM2902 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. IMM2902 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 IMM2902 to CD47 on healthy
hematopoietic stem cells (HSCs) and may minimize any associated adverse effects.;
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
