Preferred Label : Anti-CD47/Anti-mesothelin Bispecific Antibody NI-1801;
NCIt synonyms : Bispecific Mesothelin x CD47 Engaging Antibody NI-1801; Anti-CD47/Anti-MSLN Bispecific Antibody NI-1801; Anti-Mesothelin/Anti-CD47 Bispecific Antibody NI-1801;
NCIt definition : An immunoglobulin G1 (IgG1) bispecific human antibody directed against the human tumor-associated
antigen (TAA) mesothelin (MSLN) and the human cell surface antigen CD47, with potential
immunostimulating, phagocytosis-inducing and antineoplastic activities. Upon administration
of anti-CD47/anti-MSLN bispecific antibody NI-1801, the anti-MSLN arm selectively
targets and binds to MSLN expressed on MSLN-positive cancer cells, thereby improving
specific binding of the anti-CD47 arm to the MSLN-expressing cancer cells. The CD47
binding by NI-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 MSLN/CD47-expressing tumor cells. Additionally, blocking CD47 signaling activates
an anti-tumor T-lymphocyte immune response and T-cell-mediated killing of MSLN/CD47-expressing
tumor cells. In addition, NI-1801 induces an anti-tumor activity through the induction
of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular
phagocytosis (ADCP). 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. By co-targeting
CD47 and MSLN, NI-1801 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.
MSLN is overexpressed by a variety of cancer cell types.;
Molecule name : NI 1801; NI-1801;
NCI Metathesaurus CUI : CL1793063;
Origin ID : C188247;
UMLS CUI : C5706478;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
