Preferred Label : Anti-GARP/PD-L1 Bispecific Antibody BPB-101;
NCIt synonyms : GARP x PD-L1 Bispecific Antibody BPB-101; Anti-GARP/Anti-PD-L1 Bispecific Antibody BPB-101;
NCIt definition : An immunoglobulin G1 (IgG1) humanized bispecific antibody directed against the transforming
growth factor beta (TGFbeta) activator glycoprotein A repetitions predominant (GARP;
leucine-rich repeat-containing protein 32; LRRC32) and the immunosuppressive ligand
programmed cell death-1 ligand 1 (PD-L1; PDL1; cluster of differentiation 274; CD274),
with potential immune checkpoint inhibitory, immunomodulating and antineoplastic activities.
Upon administration, anti-GARP/PD-L1 bispecific antibody BPB-101 selectively targets
and binds to GARP. This specifically blocks the GARP-mediated release of the cytokine
transforming growth factor-beta 1 (TGF-b1) from the GARP-TGFbeta complex (small latent
complex; SLC) and neutralizes free/mature TGF-beta, thereby relieving the immunosuppression
caused by TGF-b1 and reversing the immunosuppressive nature in the tumor microenvironment
(TME). This improves anti-tumor immune responses. BPB-101 simultaneously targets,
binds to, and inhibits the activity of PD-L1 on tumor cells, blocking its binding
to and activation of its receptor programmed cell death 1 (PD-1; cluster of differentiation
279; CD279). This reverses T-cell inactivation caused by PD-1/PD-L1 signaling and
enhances the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against
PD-L1-expressing tumor cells. This prevents both TGF-beta- and PD-L1-mediated immuno-suppressive
pathways signaling, inhibits the negative regulatory function of regulatory T-cells
(Tregs) and increases natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activities.
This restores and enhances anti-tumor responses and inhibits tumor cell proliferation
in susceptible tumor cells. GARP, a transmembrane protein highly expressed on activated,
immunosuppressive Tregs) in the TME, is essential for the expression of TGF-b1 on
the cell surface of activated Tregs; it plays an important role in regulation of the
immune cell function and the immunosuppressive nature of Tregs. TGF-b1 stimulates
stromal cell proliferation, neovascularization, cancer cell metastasis, and inhibits
immune cell infiltration. PD-L1 is overexpressed by many human cancer cell types.
PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in immune
evasion. PD-1, a transmembrane protein belonging to the immunoglobulin superfamily
(IgSF) expressed on activated T-cells, is a negative regulator of the immune system
that limits the expansion and survival of CD8-positive T-cells.;
Molecule name : BPB-101; BPB 101;
Origin ID : C200800;
chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
