Preferred Label : Lucorafusp Alfa;
NCIt synonyms : TIGIT/TGF-beta Dual-targeting Antibody Fusion Protein AK130; Anti-TIGIT Antibody/TGFbeta-RII 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 lucorafusp alfa, 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.;
UNII : M55KSH2AGH;
CAS number : 2769742-99-4;
Molecule name : AK-130; AK 130;
NCI Metathesaurus CUI : CL1906412;
Origin ID : C198990;
UMLS CUI : C5854391;
Semantic type(s)
- concept_is_in_subset
- has_target
