nivolumab and hyaluronidase-nvhy

A co-formulation composed of nivolumab, a fully human immunoglobulin G4 (IgG4) monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death protein 1 (PD-1; PDCD1; CD279), and a recombinant form of human hyaluronidase, with potential immune checkpoint inhibitory and antineoplastic activities. Upon subcutaneous administration of nivolumab and hyaluronidase-nvhy, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity. Hyaluronidase hydrolyzes and degrades the glycosaminoglycan hyaluronic acid (HA), thereby decreasing interstitial viscosity and enhancing penetration of nivolumab through the interstitial space. This facilitates the delivery of nivolumab.