anti-PVR monoclonal antibody NTX-1088

An immunoglobulin G4 (IgG4) monoclonal antibody targeting the poliovirus receptor (PVR; CD155; nectin-like protein 5; NECL-5), with potential immune checkpoint inhibitory, immunostimulatory and antineoplastic activities. Upon administration, anti-PVR monoclonal antibody NTX-1088 targets and binds to PVR expressed on tumor cells, thereby preventing its interactions with the human cell surface glycoprotein CD226 (DNAX accessory molecule-1; DNAM-1), 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). The binding of NTX-1088 to CD226 prevents the internalization of CD226 and restores its expression on the surface of immune cells. This promotes CD226-dependent signaling pathways, which may trigger the activation of antigen-presenting cells (APCs) and activate T cells and natural killer (NK) cells, and result in an enhanced cytotoxic T-lymphocyte (CTL)-mediated and NK cell-mediated immune response against tumor cells. The binding of NTX-1088 to TIGIT expressed on various immune cells, particularly on tumor-infiltrating lymphocytes (TILs), prevents the interaction of TIGIT with its ligands and promotes the interaction of its ligands with the costimulatory receptor CD226 expressed on immune cells. This leads to CD226 dimerization and further promotes CD226-mediated signaling and anti-tumor immune responses. The binding of NTX-1088 to CD96 expressed primarily on T cells and NK cells prevents its downstream signaling pathways. This may abrogate CD96-mediated inhibition of T-cell and NK-cell effector function and may further restore immune function and anti-tumor immune responses through the activation of T cells and NK cells. PVR, a key regulator of immune activation through multiple mechanisms, is overexpressed in a variety of tumor cell types while minimally or not expressed in normal tissues.