Anti-Human PD-1 (Genolimzumab) (P440-GRP)

PD-1 is a transmembrane protein in the CD28/CTLA-4 subfamily of the Ig superfamily 1,2. When stimulated via the T cell receptor (TCR), Tregs translocate PD-1 to the cell surface 3. Programmed cell death 1 ligand 1 (PD-L1; CD274; B7H1) and programmed cell death 1 ligand 2 (PD-L2; CD273; B7DC) have been identified as PD-1 ligands 1. PD-1 is co-expressed with PD-L1 on tumor cells and tumor-infiltrating antigen-presenting cells (APCs) 2. Additionally, PD-1 is co-expressed with IL2RA on activated CD4+ T cells 3. PD-1 is an immune checkpoint receptor that suppresses cancer-specific immune responses 4. Additionally, PD-1 acts as a T cell inhibitory receptor and plays a critical role in peripheral tolerance induction and autoimmune disease prevention as well as important roles in the survival of dendritic cells, macrophage phagocytosis, and tumor cell glycolysis 2. PD-1 prevents uncontrolled T cell activity, leading to attenuation of T cell proliferation, cytokine production, and cytolytic activities. Additionally, the PD-1 pathway is a major mechanism of tumor immune evasion, and, as such, PD-1 is a target of cancer immunotherapy 2. Genolimzumab is a humanized IgG4 monoclonal antibody that targets PD-1 and prevents binding to PD-L1 and PD-L2 ligands, allowing T cell activation and tumor cell death 5,6. Genolimzumab has very low antibody-dependent cell mediated cytotoxicity and complement-dependent cytotoxicity 5. Genolimzumab does not completely block nivolumab or pembrolizumab binding to PD-1, suggesting the use of a novel binding epitope 6. Anti-tumor activity has been demonstrated in various clinical trials5.