Preferred Label : Anti-CD38/Anti-CD47 Bispecific Antibody ISB 1442;
NCIt synonyms : CD38 x CD47 Bispecific Antibody ISB 1442; Anti-CD38/CD47 Bispecific Antibody ISB 1442;
NCIt definition : A human bispecific antibody directed against the human cell surface glycoproteins
CD38 and CD47, with potential immunostimulating, phagocytosis-inducing and antineoplastic
activities. Upon administration, the biparatopic anti-CD38 moiety of anti-CD38/anti-CD47
bispecific antibody ISB 1442 targets and binds to different regions of CD38 on CD38-expressing
tumor cells, and enables the binding of the anti-CD47 moiety to CD38/CD47-expressing
tumor cells. The CD47 binding by ISB 1442 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 CD38/CD47-expressing tumor cells. In addition, the CD38 binding
by ISB 1442 may trigger antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent
cell mediated phagocytosis (ADCP) and antibody-mediated complement dependent cytotoxicity
(CDC) in CD38-expressing tumor cells. 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.
CD38, a type II transmembrane glycoprotein, is present on various immune cells and
hematologic malignancies. ISB 1442 enables CD47 binding only upon CD38 crosslinking.
This may prevent side effects that would have resulted from the binding of the anti-CD47
moiety to CD47 expressed on healthy hematopoietic stem cells (HSCs).;
Molecule name : ISB 1442; ISB-1442;
NCI Metathesaurus CUI : CL1793604;
Origin ID : C188360;
UMLS CUI : C5706493;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
