Definition

An inhibitor of T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), a co-inhibitory molecule and immune checkpoint inhibitor, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, TIGIT inhibitor M6223 targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T-lymphocytes (TILs), thereby preventing 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. 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.