Definition

A self-delivering small-interfering RNA (siRNA) targeting the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279), with potential immune checkpoint inhibitory and antineoplastic activities. Upon intratumoral administration, anti-PD-1 siRNA PH-762 binds to and destroys mRNA PD-1, thereby preventing the expression of PD-1. As PD1-mediates the downregulation of T-cell activation and proliferation, PH-762 is able to restore immune function and activates a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. This may lead to an inhibition of tumor cell proliferation. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands PD-L1 (cluster of differentiation 274; CD274) or 2 (PD-L2; CD273); it plays an important role in tumor evasion from host immunity.