Mimotopes to Cetuximab Isolated by mRNA-Display using Random Peptide Libraries and their Characteristics

To obtain epitope mimic peptides, mimotopes, for vaccine development, mRNA display technology was applied to Cetuximab. After six cycles of affinity selection, four clones that bound to Cetuximab were isolated that showed specific binding to the antibody in pull-down assays. Their random peptide portions were chemically synthesized and conjugated with keyhole limpet hemocyanin (KLH). Their ability to elicit production of antibodies that bind to the antibody’s original antigen, the human EGF receptor, was examined by vaccination in rabbits five times bi-weekly. Although the peptides and their KLH conjugates showed different characteristics in vitro and further analysis is needed, the results of immunizations showed that the mimotope peptides isolated from mRNA display libraries could generate antibodies against the antibody’s original antigen in vivo.