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- NCIT_C188247 IAO_0000115 "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." @default.
- NCIT_C188247 NCIT_A7 NCIT_C20887 @default.
- NCIT_C188247 NCIT_A7 NCIT_C25795 @default.
- NCIT_C188247 NCIT_NHC0 "C188247" @default.
- NCIT_C188247 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C188247 NCIT_P108 "Anti-CD47/Anti-mesothelin Bispecific Antibody NI-1801" @default.
- NCIT_C188247 NCIT_P208 "CL1793063" @default.
- NCIT_C188247 NCIT_P322 "GDC" @default.
- NCIT_C188247 NCIT_P399 "810064" @default.
- NCIT_C188247 NCIT_R124 NCIT_C17710 @default.
- NCIT_C188247 NCIT_R124 NCIT_C17828 @default.
- NCIT_C188247 NCIT_R124 NCIT_C18219 @default.
- NCIT_C188247 NCIT_R124 NCIT_C19986 @default.
- NCIT_C188247 NCIT_R124 NCIT_C40474 @default.
- NCIT_C188247 normalizedInformationContent "100" @default.
- NCIT_C188247 referenceCount "1" @default.
- NCIT_C188247 hasExactSynonym "Anti-CD47/Anti-MSLN Bispecific Antibody NI-1801" @default.
- NCIT_C188247 hasExactSynonym "Anti-CD47/Anti-mesothelin Bispecific Antibody NI-1801" @default.
- NCIT_C188247 hasExactSynonym "Anti-Mesothelin/Anti-CD47 Bispecific Antibody NI-1801" @default.
- NCIT_C188247 hasExactSynonym "Bispecific Mesothelin x CD47 Engaging Antibody NI-1801" @default.
- NCIT_C188247 hasExactSynonym "NI 1801" @default.
- NCIT_C188247 hasExactSynonym "NI-1801" @default.
- NCIT_C188247 hasExactSynonym "NI1801" @default.
- NCIT_C188247 inSubset NCIT_C128784 @default.
- NCIT_C188247 inSubset NCIT_C157711 @default.
- NCIT_C188247 inSubset NCIT_C157712 @default.
- NCIT_C188247 inSubset NCIT_C176424 @default.
- NCIT_C188247 type Class @default.
- NCIT_C188247 isDefinedBy ncit.owl @default.
- NCIT_C188247 label "Anti-CD47/Anti-mesothelin Bispecific Antibody NI-1801" @default.
- NCIT_C188247 subClassOf NCIT_C129821 @default.
- NCIT_C188247 subClassOf NCIT_C129822 @default.
- NCIT_C188247 subClassOf NCIT_C1454 @default.
- NCIT_C188247 subClassOf NCIT_C159583 @default.
- NCIT_C188247 subClassOf NCIT_C163758 @default.
- NCIT_C188247 subClassOf NCIT_C188247 @default.
- NCIT_C188247 subClassOf NCIT_C1908 @default.
- NCIT_C188247 subClassOf NCIT_C1909 @default.
- NCIT_C188247 subClassOf NCIT_C192655 @default.
- NCIT_C188247 subClassOf NCIT_C201534 @default.
- NCIT_C188247 subClassOf NCIT_C20401 @default.
- NCIT_C188247 subClassOf NCIT_C274 @default.
- NCIT_C188247 subClassOf NCIT_C28227 @default.
- NCIT_C188247 subClassOf NCIT_C307 @default.
- NCIT_C188247 subClassOf NCIT_C308 @default.