Preferred Label : Zeripatamig;
NCIt synonyms : Bispecific Monoclonal Antibody TG-1801; Anti-CD47/CD19 Bispecific Monoclonal Antibody TG-1801;
NCIt definition : A bispecific monoclonal antibody composed of two single-chain variable fragments (scFv),
one directed against the B-cell-specific membrane protein CD19, and another that is
directed against the human cell surface antigen CD47, with potential immunostimulating,
phagocytosis-inducing and antineoplastic activities. Upon administration of zeripatamig,
the anti-CD19 moiety selectively targets and binds to CD19 on CD19-positive B-cells,
thereby improving binding of the anti-CD47 moiety to the CD19 malignant B-cells.
The CD47 binding by TG-1801 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 CD19/CD47-expressing tumor cells. Additionally, blocking CD47 signaling activates
an anti-tumor T-lymphocyte immune response and T-cell-mediated killing of CD19/CD47-expressing
tumor cells. In addition, zeripatamig induces an anti-tumor activity through the induction
of antibody dependent cellular cytotoxicity (ADCC). CD47, also called integrin-associated
protein (IAP), is a tumor-associated antigen (TAA), 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. CD19 is a membrane antigen that is widely
expressed during B-cell development and in B-cell malignancies. By co-targeting CD47
and CD19, zeripatamig 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 : BK3WC9ZP7A;
CAS number : 2607644-43-7;
Molecule name : TG-1801; TG 1801;
NCI Metathesaurus CUI : CL979205;
Origin ID : C166137;
UMLS CUI : C5706659;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
