Single Biggest Cancer Dictionary in the World

What is anti-CD47/anti-mesothelin bispecific antibody NI-1801?

Pronunciation: /ˈænˌti ˈsiˈdi forty-seven* ˈænˌti mesothelin* bispecific* ˈæntɪˌbɑdi ni wən ˈθaʊzənd, eɪt ˈhənərd ənd wən/

anti-CD47/anti-mesothelin bispecific antibody NI-1801

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.