Preferred Label : Peluntamig;
NCIt synonyms : Anti-DLL3/CD47 Bispecific Antibody PT217; DLL3 x CD47 Bispecific Antibody PT217; Anti-DLL3/Anti-CD47 Bispecific Antibody PT217;
NCIt definition : A bispecific antibody directed against both the tumor-associated antigen (TAA) delta-like
protein 3 (DLL3) and the human cell surface antigen CD47, with potential immunostimulating,
phagocytosis-inducing and antineoplastic activities. Upon administration of peluntamig,
the anti-DLL3 moiety selectively targets and binds to DLL3 on DLL3-expressing tumor
cells, thereby improving the binding of the anti-CD47 moiety to DLL3-expressing tumor
cells. The CD47 binding by PT217 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 DLL3-expressing tumor cells. Additionally, blocking CD47 signaling activates an
anti-tumor T-lymphocyte immune response and T-cell-mediated killing of DLL3-expressing
tumor cells. PT217 may also induce 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 (RBCs) 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. DLL3, a Notch pathway
protein, is overexpressed on a variety of cancer cell types. It plays a key role in
embryonic development and in tumor initiation and proliferation. Co-targeting CD47
and DLL3 may limit the binding of PT217 to CD47 on healthy hematopoietic stem cells
(HSCs) and may minimize the associated adverse effects.;
UNII : 4A6ZWS8R8E;
CAS number : 2928515-21-1;
Molecule name : PT 217; PT-217;
NCI Metathesaurus CUI : CL1906227;
Origin ID : C199289;
UMLS CUI : C5853679;
Semantic type(s)
chemical_or_drug_has_mechanism_of_action
concept_is_in_subset
has_target