Definition

A Fc-enhanced 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 an as of yet undisclosed receptor expressed specifically on T cells and natural killer (NK) cells, with potential immune checkpoint inhibitory, immunomodulating and antineoplastic activities. Upon administration, the anti-TIGIT bispecific antibody BMS-986442 simultaneously targets and binds to TIGIT and the undisclosed receptor. Upon binding to TIGIT expressed on various immune cells, particularly on tumor-infiltrating lymphocytes (TILs), BMS-986442 blocks 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 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, binding of BMS-986442 to the undisclosed target expressed on T cells and NK cells may further enhance anti-tumor immune responses. 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.