Preferred Label : Anti-TIGIT Antibody/TGFbeta-RII Fusion Protein AK130;
NCIt synonyms : TIGIT/TGF-beta Dual-targeting Antibody Fusion Protein AK130;
NCIt definition : A bifunctional fusion protein composed of a humanized Fc-mutant anti-T-cell immunoreceptor
with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT)
antibody fused to transforming growth factor beta (TGF-beta) receptor type II (TGFbetaRII),
with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration
of anti-TIGIT antibody/TGFbeta-RII fusion protein AK130, the TGFbetaRII moiety targets,
binds to and neutralizes TGF-beta while the anti-TIGIT antibody moiety simultaneously
targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating
lymphocytes (TILs) and natural killer (NK) cells. The neutralization of TGF-beta prevents
TGF-beta-mediated immunosuppressive signaling, thereby enhancing anti-tumor immunity
in the tumor microenvironment (TME). The binding to TIGIT 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), and enhances
the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory
molecule-1; DNAM-1) expressed on immune cells, such as 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. TIGIT, a member
of the Ig superfamily (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. TGF-beta, dysregulated
in many types of cancer, plays a key role in immunosuppression in the TME and is involved
in tumor cell proliferation and tumor progression. The mutations in the Fc region
of the anti-TIGIT antibody moiety prevent antibody-dependent cell-mediated cytotoxicity
(ADCC) and complement-dependent cytotoxicity (CDC), and the resulting loss of lymphocytes.;
Molecule name : AK-130; AK 130;
NCI Metathesaurus CUI : CL1906412;
Origin ID : C198990;
concept_is_in_subset
- has_target
