RBCs-anti-PD1 antibody conjugate WTX212

A preparation of autologous engineered red blood cells (RBCs) conjugated with pembrolizumab, an antibody against the negative immunoregulatory human cell receptor programmed cell death protein 1 (PD-1; PDCD1; CD279), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration of the RBCs-anti-PD1 antibody conjugate WTX212, the RBCs primarily and directly distribute to the spleen and vascular system. The anti-PD1 antibodies target, bind to and inhibit PD-1, leading to the abrogation of PD1-mediated downregulation of T-cell activation and proliferation. This restores immune function, decreases programmed cell death-1 ligand 1 (PD-L1)-positive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) and activates a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. 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.