Preferred Label : Anti-DLL3/Anti-CD47 Bispecific Antibody PT217;
NCIt synonyms : Anti-DLL3/CD47 Bispecific Antibody PT217; DLL3 x 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 anti-DLL3/anti-CD47
bispecific antibody PT217, 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.;
Molecule name : PT 217; PT-217;
NCI Metathesaurus CUI : CL1906227;
Origin ID : C199289;
chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
