Preferred Label : Anti-TIGIT/Anti-PD-L1 Bispecific Antibody HLX301;
NCIt synonyms : Anti-TIGIT/PD-L1 Bispecific Antibody HLX301; TIGIT x PD-L1 Bispecific Antibody HLX301;
NCIt definition : A bispecific antibody directed against both the co-inhibitory molecule and immune
checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor
tyrosine-based inhibitory motif (ITIM) domains (TIGIT) and the immunosuppressive ligand
programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with
potential immune checkpoint inhibitory and antineoplastic activities. Upon administration,
the anti-TIGIT/anti-PD-L1 bispecific antibody HLX301 simultaneously targets, binds
to and inhibits TIGIT and PD-L1, thereby inhibiting their downstream signaling pathways.
Inhibition of TIGIT expressed on various immune cells, particularly on tumor-infiltrating
lymphocytes (TILs), prevents the interaction of TIGIT with its ligands CD112 (nectin-2;
poliovirus receptor related-2; PRR2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like
protein 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory
receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells,
such as natural killer (NK) cells and CD8 T-cells. This leads to CD226 dimerization
and CD226-mediated signaling and activates the immune system to exert a T-cell-mediated
immune response against cancer cells. Inhibition of PD-L1 prevents its binding to
and activation of 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. TIGIT, a member of the Ig super family (IgSF) and an immune inhibitory
receptor, plays a key role in the suppression of T-cell proliferation and activation;
it is involved in tumor cell immune evasion, and the inhibition of antiviral immune
responses. 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.;
Molecule name : HLX 301; HLX-301;
NCI Metathesaurus CUI : CL1773507;
Origin ID : C185160;
UMLS CUI : C5666953;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
