A mimotope peptide-based anti-cancer vaccine selected by BAT monoclonal antibody

Combinatorial phage display peptide libraries are employed to identify small molecules which bind with high affinity to receptor molecules and which mimic the interaction with natural ligands. We used a synthetic combinatory phage display peptide library to screen for peptides that bind BAT monoclonal antibody, an immune modulatory and anti-tumor antibody, to serve as the basis for an anti-cancer vaccine. Two distinct mimotopes, peptides A and B, were isolated, with repeated Proline, Arginine, and Isoleucine amino acids. Mimotope binding was determined by direct binding and by inhibition of BAT binding to the peptide bound phages and to Daudi cells. Immunization of mice with the peptides induced cellular and humoral responses. Cellular response was manifested by significant increase in cytolitic activity. Humoral response was manifested by production of specific antibodies. Serum purified IgG fraction contained anti-peptide antibodies that identified BAT binding mimotopes and competed with BAT binding on Daudi cells. These BAT like antibodies exhibited similar immune stimulatory properties to BAT. Immunization of mice with the peptides prevented tumor growth. These finding are the basis for the development of an anti-cancer vaccine. (c) 2005 Elsevier Ltd. All rights reserved.