Anti-HER2 vaccines: new prospects for breast cancer therapy

Each year, breast cancer accounts for more than 400,000 new cancer cases and more than 130,000 cancer deaths in Europe. Prognosis of nonmetastatic breast cancer patients is directly related to the extent of the disease, mainly nodal spreading and tumor size, and to the molecular profile, particularly HER2 over-expression. In patients with HER2-over-expressing tumors, different studies have shown cellular and/or humoral immune responses against HER2 associated with a lower tumor development at early stages of the disease. These findings have led to the hypothesis that the generation of an anti-HER2 immune response should protect patients from HER2-over-expressing tumor growth. Taken together with the clinical efficiency of trastuzumab-based anti-HER2 passive immunotherapy, these observations allowed to envisage various vaccine strategies against HER2. The induction of a stable and strong immunity by cancer vaccines is expected to lead to establishment of immune memory, thereby preventing tumor recurrence. However, an immunological tolerance against HER2 antigen exists representing a barrier to effective vaccination against this oncoprotein. As a consequence, the current challenge for vaccines is to find the best conditions to break this immunological tolerance. In this review, we will discuss the different anti-HER2 vaccine strategies currently developed; considering the strategies having reached the clinical phases as well as those still in preclinical development. The used antigen can be either composed of tumoral allogenic cells or autologous cells, or specific to HER2. It can be delivered by dendritic cells or in a DNA, peptidic or proteic form. Another area of research concerns the use of anti-idiotypic antibodies mimicking HER2.