DISCOVERY OF ANTI-LAG-3 PEPTIDES AND CONSTRUCTION OF A HYBRID SINGLE-DOMAIN ANTIBODY PHAGE DISPLAY LIBRARY FOR CANCER IMMUNOTHERAPY

Abstract

Cancer immunotherapy is transforming the way we treat cancer. Instead of targeting cancers directly, immunotherapy utilizes the body's immune system to identify and eliminate cancer cells. This approach offers promise for more effective and less harmful treatments than traditional methods, representing a significant advancement in cancer care. There are two primary objectives in this dissertation. The first research objective is to discover peptide inhibitors of lymphocyte activation gene 3 (LAG-3) using phage display biopanning technology. Blocking the LAG-3 interaction with its ligand, fibrinogen-like protein 1 (FGL1), can potentially restore the T cell’s antitumor function to eliminate cancer cells. Combining these inhibitors with other therapies may help overcome resistance that develops against immune checkpoint treatments. The second research objective is to construct a hybrid single-domain antibody phage display library. Successful completion of this project will establish a novel method to construct a single-domain antibody library that can be used to discover sdAbs with high affinity and specificity for the antigen of interest.