recombinant human hyaluronidase and pembrolizumab

A fixed-dose co-formulation composed of pembrolizumab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody directed against human cell surface receptor PD-1 (programmed death-1; programmed cell death-1; cluster of differentiation 279; CD279), and MK-5180, a recombinant form of human hyaluronidase, with potential immune checkpoint inhibitory and antineoplastic activities. Upon subcutaneous administration of recombinant human hyaluronidase and pembrolizumab, the hyaluronidase reversibly depolymerizes the polysaccharide hyaluronan in the subcutaneous tissue. This increases the permeability of the subcutaneous tissue and enhances the absorption of pembrolizumab into the systemic circulation. In turn, pembrolizumab 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; cluster of differentiation 274; CD274), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. When administered subcutaneously, hyaluronidase, an endoglycosidase, increases the dispersion and absorption of co-administered drugs.