Preferred Label : Anti-PD-L1/CD137 Bispecific Antibody MCLA-145;
NCIt synonyms : Anti-PD-L1/Anti-CD137 Bispecific Antibody MCLA-145; Anti-PD-L1/4-1BB Bispecific Antibody MCLA-145;
NCIt definition : A full-length, Fc-silenced immunoglobulin G1 (IgG1) bispecific antibody targeting
both the human programmed death-ligand 1 (PD-L1) and CD137 (4-1BB; tumor necrosis
factor receptor superfamily member 9; TNFRSF9), with potential checkpoint inhibitory,
immunostimulating and antineoplastic activities. Upon administration, anti-PD-L1/CD137
bispecific antibody MCLA-145 simultaneously targets and binds to CD137, which is expressed
on a variety of leukocyte subsets including activated T-lymphocytes, and PD-L1 expressed
on tumor cells, thereby crosslinking PD-L1-expressing tumor cells and T-lymphocytes.
Through CD137 binding, MCLA-145 acts as a conditional CD137 agonist, resulting in
T-cell co-stimulation and enhanced anti-tumor activity. At the same time, MCLA-145
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. CD137, 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. Crosslinking
of PD-L1-expressing tumor cells and activated T-lymphocytes may enhance T-lymphocyte-mediated
lysis of PD-L1-expressing tumor cells.;
Molecule name : MCLA-145; MCLA 145;
NCI Metathesaurus CUI : CL969758;
Origin ID : C160772;
UMLS CUI : C5205540;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
