alpha-PD1/IL2 fusion protein AWT020

A bifunctional fusion protein comprised of a monoclonal antibody directed against the human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) linked to an engineered, variant form of interleukin-2 (IL-2) and IL2c mutein (No-alpha-IL-2), with potential immunostimulating and antineoplastic activities. Upon administration of anti-PD-1-IL-2 fusion protein AWT020, the antibody moiety specifically targets, binds to and blocks PD-1 expressed on tumor-infiltrating lymphocytes (TILs) and thereby brings the IL-2 moiety to PD-1-expressing tumoral T cells. The IL-2 moiety binds to the interleukin-2 receptor (IL2R), activates pSTAT5, and may activate and expand tumor-infiltrating T cells. This may enhance the activity of cytotoxic T cells and potentiates T-cell-mediated immune responses 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, programmed cell death-1 ligand 1 (PD-L1; B7-H1; CD274) and 2 (PD-L2); it plays an important role in tumor evasion from host immunity. No-alpha-IL-2 cannot bind to IL-2 receptor-alpha (CD25, IL2Ra) and does not activate regulatory T cells (Tregs).