Preferred Label : Anti-TIGIT/Anti-PVRIG Bispecific Antibody SIM0348;
NCIt synonyms : Anti-TIGIT/PVRIG Bispecific Antibody SIM0348; TIGIT x PVRIG Bispecific Antibody SIM0348; Anti-PVRIG/Anti-TIGIT Bispecific Antibody SIM0348;
NCIt definition : A humanized immunoglobulin G1 (IgG1)-based 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 poliovirus receptor-related immunoglobulin (PVRIG; PVR Related Immunoglobulin
Domain Containing Protein; CD112R), with potential immune checkpoint inhibitory and
antineoplastic activities. Upon administration, the anti-TIGIT/anti-PVRIG bispecific
antibody SIM0348 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 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. In addition, SIM0348 induces Fc-mediated killing
of TIGIT-expressing immunosuppressive regulatory T-cells (Tregs) and Tregs expressing
TIGIT and PVRIG. TIGIT, a member of the immunoglobulin 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 : SIM 0348; SIM-0348;
NCI Metathesaurus CUI : CL1906949;
Origin ID : C200115;
UMLS CUI : C5854474;
Semantic type(s)
- chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
