Preferred Label : Anti-CD47/CD20 Bispecific Antibody CC-96673;
NCIt synonyms : Anti-CD47/Anti-CD20 Bispecific Antibody CC-96673; Anti-CD20/CD47 Bispecific Antibody CC-96673; CD47 x CD20 Bispecific Antibody CC-96673;
NCIt definition : A humanized immunoglobulin G1 (IgG1) affinity-tuned 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 anti-CD47/CD20 bispecific antibody
CC-96673, the anti-CD20 moiety selectively targets and binds with high affinity to
CD20 on CD20-positive B-cells, and the anti-CD47 moiety targets and binds with optimally
lowered affinity to CD47 expressed on the CD20-positive malignant B-cells. The CD47
binding by CC-96673 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. CC-96673 may also induce an anti-tumor activity through the induction
of antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity
(CDC) against CD20-positive tumor cells. CD20 is a non-glycosylated cell surface phosphoprotein
which is exclusively expressed on B-cells during most stages of B-cell development.
It is often overexpressed in B-cell malignancies. 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.;
Molecule name : BMS 986358; CC 96673; CC-96673; BMS-986358;
NCI Metathesaurus CUI : CL1926579;
Origin ID : C204503;
UMLS CUI : C5908053;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
