Preferred Label : Amulirafusp Alfa;
NCIt synonyms : Anti-CD20/CD47 mAb-Trap IMM0306; Anti-CD20/CD47 Antibody Receptor Recombinant Protein IMM0306; Anti-CD47/CD20 Bispecific Antibody IMM0306;
NCIt definition : A bispecific antibody directed against both the B-cell-specific membrane protein and
tumor-associated antigen (TAA) CD20, and the human cell surface antigen CD47, with
potential immunostimulating, phagocytosis-inducing and antineoplastic activities.
Upon administration of amulirafusp alfa, the anti-CD20 moiety selectively targets
and binds to CD20 on CD20-positive B-cells, thereby improving the binding of the anti-CD47
moiety to the CD20-positive malignant B-cells. The CD47 binding by amulirafusp 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 CD20/CD47-expressing
tumor cells. Additionally, blocking CD47 signaling activates an anti-tumor T-lymphocyte
immune response and T-cell-mediated killing of CD20/CD47-expressing tumor cells. In
addition, amulirafusp alfa induces 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. CD20 is a membrane antigen that is overexpressed in B-cell malignancies.
By co-targeting CD47 and CD20, amulirafusp alfa has the potential to overcome the
limitations of existing CD47-targeted therapies by possibly avoiding the side effects
caused by binding to CD47 on healthy hematopoietic stem cells (HSCs) which causes
unwanted macrophage-mediated phagocytosis.;
UNII : HFR7WU5YK7;
CAS number : 2850355-94-9;
Molecule name : IMM 0306; IMM-0306;
NCI Metathesaurus CUI : CL1662429;
Origin ID : C179653;
UMLS CUI : C5555844;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
