Knowledge about which epitopes are recognized by a blocking antibody can help researchers to develop improved antibodies for drug discovery and to better understand the mechanism of inhibition.
The binding of Programmed Cell Death Protein 1 (PD-1), one of the receptors expressed on activated T-cells (see Figure 1), to its ligands PD-L1 and PD-L2, negatively regulates immune responses. PD-1 ligands are found on most cancers, and PD-1:PD-L1/2 interaction inhibits T cell activity and allows cancer cells to escape immune surveillance.
The first therapeutic antibodies in this field have been directed against the checkpoint receptor PD-1 (Nivolumab by Bristol Myers Squibb and Pembrolizumab by Merck/MSD). The drugs have been approved for the treatment of diverse cancer types during the past years. The PD-1:PD-L1/2 pathway is also involved in regulating autoimmune responses, making these proteins promising therapeutic targets for a number of cancers, as well as multiple sclerosis, arthritis, lupus, and type I diabetes. Further research projects in this field are rapidly evolving as scientists seek to identify the next generation of therapies especially developing therapies combining different therapeutic approaches.
The treatment of diseases by inducing, enhancing, or surpressing an immune response is referred to as Immunotherapy. Therapeutic manipulation of immunopathways has led to promising clinical results for the treatment of a number of diseases. The first therapeutic antibodies directed against the checkpoint receptor PD-1 have been already brought to the market (Nivolumab, Pembrolizumab) by Bristol Myers Squibb and Merck/MSD respectively, and approved for the treatment of diverse cancer types.
Today, I would like to review a versatile tool to conduct cell based inhibitor screenings on PD-1 / PD-L1/PD-L2 binding.