Preferred Label : Anti-4-1BB/PD-L1 Bispecific Antibody PM1003;
NCIt synonyms : Anti-PD-L1/4-1BB Bispecific Antibody PM1003; Anti-4-1BB/Anti-PD-L1 Monoclonal Antibody PM1003; 4-1BB x PD-L1 Bispecific Antibody PM1003;
NCIt definition : A VHH-based bispecific antibody targeting human programmed death-ligand 1 (PD-L1)
and 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with
potential checkpoint inhibitory, immunostimulating and antineoplastic activities.
Upon administration, anti-4-1BB/PD-L1 bispecific antibody PM1003 simultaneously targets
and binds, with its anti-4-1BB VHH arm, to an epitope at the CRD4 region of 4-1BB,
which is expressed on a variety of leukocyte subsets including activated T-lymphocytes,
and, with its anti-PD-L1 VHH arm, to an epitope that overlaps with the binding region
of PD-1 on PD-L1, which is expressed on tumor cells. Upon PD-L1 binding and PD-L1-mediated
cross-linking, the 4-1BB activation signal is induced and PM1003 acts as a conditional
4-1BB agonist in the tumor microenvironment (TME), resulting in T-cell co-stimulation
and enhances T-lymphocyte-mediated anti-tumor activity. At the same time, PM1003 prevents
PD-L1 from binding to and activating its receptor, programmed cell death 1 (PD-1;
PDCD1; CD279; programmed death-1). 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 : PM 1003; PM-1003;
Origin ID : C200793;
concept_is_in_subset
- has_target
