PD-1 Targeted Antibody Discovery Using AI Protein Diffusion

Abstract

AbstractThe programmed cell death protein 1 (PD-1, CD279) is an important therapeutic target in many oncological diseases. This checkpoint protein inhibits T lymphocytes from attacking other cells in the body and thus blocking it improves the clearance of tumor cells by the immune system. While there are already multiple FDA-approved anti-PD-1 antibodies, including nivolumab (Opdivo® from Bristol-Myers Squibb) and pembrolizumab (Keytruda® from Merck), there are ongoing efforts to discover new and improved checkpoint inhibitor therapeutics. In this study, we present multiple anti-PD-1 antibody fragments that were derived computationally using protein diffusion and evaluated through our scalable,in silicopipeline. Here we present nine synthetic Fv structures that are suitable for further empirical testing of their anti-PD-1 activity due to desirable predicted binding performance.