Screening of Human Epidermal Growth Factor Receptor 2 (HER2) Extracellular Domain for Potential Epitopes by Using Immuno-informatics Tools

Abstract

The human epidermal growth factor receptor 2 (HER2) is a well-studied oncoprotein that is overexpressed in a considerable proportion of breast cancer patients. The increased expression of this tyrosine kinase receptor is usually associated with poor clinical prognosis in female patients with breast cancer. In these patients, specific response of immune system against HER2 had been observed. This suggests that immunotherapy approaches can be employed for enhancing the response of tumor infiltrating lymphocytes against HER2 in susceptible tumor microenvironment. In this regard, peptide vaccines are considered one of the most affordable immunotherapy modalities due to their low production cost and long-term effect. For this purpose, we have screened the extracellular domain of HER2 crystal for potential B-cells and T-cells epitopes by using different immuno-informatics tools. The output peptides were then refined and filtered according to their antigenicity, allergenicity and vulnerability to selected proteases. Here, we present multiple B-cells and T-cells epitope candidates against HER2 extracellular domain with high antigenicity, low allergenicity and good resistance for selected proteolytic enzymes. These filtered epitopes can be used for design and construction of anti-HER2 peptide vaccine for potential use in HER2 positive breast cancer patients. Additionally, the sequence of linear B-cells epitopes can be used for the design of monoclonal antibody variable region against HER2 extracellular domain.