Preferred Label : Anti-TIGIT/Anti-PVRIG Bispecific Antibody PM1009;
NCIt synonyms : Anti-TIGIT/PVRIG Bispecific Antibody PM1009; TIGIT x PVRIG Bispecific Antibody PM1009;
NCIt definition : A bispecific antibody composed of a human immunoglobulin G1 (IgG1) monoclonal antibody
directed against the co-inhibitory molecule and immune checkpoint inhibitor T-cell
immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory
motif (ITIM) domains (TIGIT) with a single chain variable fragment (scFv) targeting
poliovirus receptor-related immunoglobulin (PVRIG; PVR Related Immunoglobulin Domain
Containing Protein; CD112R) fused to the c-terminus, with potential immune checkpoint
inhibitory and antineoplastic activities. Upon administration, the anti-TIGIT/anti-PVRIG
bispecific antibody PM1009 simultaneously targets, binds to and inhibits TIGIT and
PVRIG and 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 PVRIG expressed on cytotoxic T-lymphocytes (CTLs)
and NK cells within the tumor microenvironment (TME) blocks the interaction of PVRIG
with its ligand nectin cell adhesion molecule 2 (poliovirus receptor-related 2; PVRL2;
CD112), which is overexpressed on a variety of tumor cell types. This abrogates the
PVRIG-mediated inhibition of T-lymphocyte and NK cell activation. This activates CTLs
and NK cells, enhances anti-tumor responses and immune-mediated tumor cell killing,
and inhibits tumor cell proliferation. 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. PVRIG, a member of the B7/CD28 family and an immune checkpoint
receptor, negatively regulates the activation of various immune cells upon activation
and plays a key role in immunosuppression.;
Molecule name : PM-1009; PM 1009;
NCI Metathesaurus CUI : CL1913088;
Origin ID : C193462;
UMLS CUI : C5785771;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
