Ponente
Descripción
HER1 and HER2 are members of the HER receptor family and are over-expressed in epithelial tumors. Several strategies, including monoclonal antibodies, have been developed against these molecules. Currently, the idea of vaccinating using HER extracellular domains (ECDs) as antigen has emerged and is supported by encouraging preclinical results. The characterization of the polyclonal response is crucial to understand the mechanism of action of the induced antibodies. In this work, we developed a methodology using phage display technology with the aim of dissecting antibody responses against HER1 and HER2 ECDs. Domains I, II, III and IV which form the complete ECD of HER1 and HER2 were displayed on phage and after immunization of mice with the respective complete ECDs, domains I, III and IV of HER1 and HER2 were recognized by antibodies, which illustrates the diversity of the response covering a wide range of antigenic regions. In addition, HER1 phage-displayed domain III variants carrying mutations that confer resistance to a monoclonal antibody in the clinical setting were recognized by polyclonal antibodies, demonstrating the superiority of the specific humoral response over monoclonal therapy. The methodology described here could be the starting point for the characterization of the humoral response elicited during cancer vaccination regimes in the future.
