vibostolimab/pembrolizumab MK-7684A

A co-formulated product containing fixed doses of the two monoclonal antibodies vibostolimab and pembrolizumab, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration of vibostolimab/pembrolizumab MK-7684A, vibostolimab, an antibody against the immune checkpoint inhibitor T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT; T-cell immunoreceptor with Ig and ITIM domains; T-cell immunoglobulin and ITIM domain), targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T lymphocytes (TILs) and natural killer (NK) cells, thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5), which are expressed on T cells, NK cells and certain cancer cells. 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, and activates CD226-mediated signaling. This activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT plays a key role in the suppression of T-cell proliferation and activation and tumor cell immune evasion. Pembrolizumab, an antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) targets and binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen presenting cells (APCs). Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity.