Design And Evaluating The Efficacy Of Novel Antibodies Enhancing Binding On CTLA-4 And PD-1 Immune Checkpoints

Immune checkpoint proteins, including CTLA-4 and PD-1, have emerged as promising targets for cancer immunotherapy due to their vital role in immune regulation. In this comprehensive study, we conducted a thorough analysis of antibody-protein interactions by employing structural analysis, mutational studies, and antibody-antigen docking simulations. Our findings revealed that antibodies 1 and 2 exhibited strong binding affinities towards CTLA-4 and PD-1 proteins, respectively. Further analysis through alanine scanning identified specific residues, namely Tyr91 on antibody 1, along with Asn31 and Asp96 on antibody 2, as potential mutation sites. Introducing these mutations resulted in the generation of two novel antibodies, 1a, 2a and 2b, which displayed enhanced binding affinity towards their respective target proteins. With their improved binding capabilities, these novel antibodies hold tremendous promise for enhancing the effectiveness of antibody-based therapies designed to target immune checkpoints in cancer treatment. The ultimate objective is to significantly improve the health outcomes of patients by leveraging the potential of these novel antibodies.