Preferred Label : Anti-PD-1/Anti-4-1BB Bispecific Antibody IBI-319;
NCIt definition : A bispecific antibody targeting both the human negative immunoregulatory checkpoint
receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and 4-1BB (CD137; tumor
necrosis factor receptor superfamily member 9; TNFRSF9), with potential checkpoint
inhibitory, immunostimulating and antineoplastic activities. Upon administration,
anti-PD-1/anti-4-1BB bispecific antibody IBI-319 simultaneously targets and binds
to PD-1, which is expressed on a variety of leukocyte subsets including activated
T-lymphocytes in the tumor microenvironment (TME), and 4-1BB, which is expressed on
activated T-lymphocytes and natural killer (NK) cells. This crosslinks PD-1- and 4-1BB-expressing
T cells. Through 4-1BB binding, IBI-319 acts as a conditional 4-1BB agonist, resulting
in T-cell co-stimulation and enhances T-lymphocyte-mediated anti-tumor activity. At
the same time, PD-1 binding prevents PD-L1 from binding to and activating its receptor
PD-1 and inhibits the PD-L1/PD-1-mediated downregulation of T-cell activation and
proliferation. This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes
and enhances cytotoxic T-cell-mediated tumor cell lysis, which may lead to a reduction
in tumor growth. PD-L1 binding to PD-1 on activated T-cells inhibits the expansion
and survival of CD8-positive T-cells, suppresses the immune system and results in
immune evasion. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor
superfamily, is an inducible costimulatory receptor that plays a key role in T-cell
proliferation, survival and cytolytic activity.;
Molecule name : IBI-319; IBI 319;
NCI Metathesaurus CUI : CL1662144;
Origin ID : C179633;
UMLS CUI : C5555829;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
