Definition

A human immunoglobulin G1 (IgG1) monoclonal antibody targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory and anti-tumor activities. Upon administration, belrestotug targets and binds to TIGIT expressed on various immune cells, including tumor-infiltrating 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. In addition, belrestotug may preferentially deplete immunosuppressive, TIGIT-expressing regulatory T-cells (Tregs) through Fc gamma receptor interaction and antibody-dependent cellular cytotoxicity (ADCC). This may further enhance anti-tumor activity. 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.