Anti-TIGIT/Anti-CD96 Bispecific Antibody BMS-986442

**Semantic type:** Amino Acid, Peptide, or Protein|Immunologic Factor|Pharmacologic Substance

**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 the negative immunoregulatory human cell surface receptor CD96 (Tactile; T cell activation increased late expression), with potential immune checkpoint inhibitory, immunomodulating and antineoplastic activities. Upon administration, anti-TIGIT/anti-CD96 bispecific antibody BMS-986442 simultaneously targets and binds to TIGIT and CD96. 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 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, BMS-986442 targets and binds to CD96 expressed on T-cells and NK cells, thereby preventing its downstream signaling pathways. This may abrogate CD96-mediated inhibition of T-cell and NK cell effector function and may restore immune function and anti-tumor immune responses through the activation of T-cells and NKs. This may further kill and inhibit the growth of tumor 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. CD96, a type I transmembrane glycoprotein of the IgSF and immunological checkpoint for CD8+ T-cells and NK cells, negatively regulates T-cell and NK cell activation and is overexpressed in a variety of cancers.

**Synonyms:** - AGEN 1777 - AGEN-1777 - AGEN1777 - Anti-TIGIT Bispecific Antibody AGEN1777 - Anti-TIGIT Bispecific Antibody BMS-986442 - BMS 986442 - BMS-986442 - BMS986442 - TIGIT Inhibitor BMS-986442