Targeting breast cancer vaccines to dendritic cells: improved immunological responses with less protein?

Despite significant advances in the treatment of Her2/neu-overexpressing breast cancer in the last few decades, the majority of patients with meta static Her2/neu+ tumors ultimately succumb to their disease. Moreover, Her2/neu proto-oncogene has generally been associated with a poor clinical outcome; however, the overexpression of this cell surface growth factor receptor also provides a target that can be exploited for immunotherapeutics. Her2/neu-specific vaccines have been tested with a further refinement in the potential effectiveness of a protein vaccine described in a paper in the previous issue of Breast Cancer Research [1]. Moreover, support for the immunotherapy approach comes from the fact that monoclonal antibody therapy (trastuzumab) improves survival in both the adjuvant [2,3] and metastatic [4] setting. However, despite improvements in clinical outcome, metastatic breast cancer remains incurable and new treatments are needed.The adoptive transfer of immune effector molecules (including monoclonal antibodies) and cells is termed passive vaccination. The success of this approach is likely dependent upon the persistence of the molecule/cell and its ability to engage the particular immunological process that results in a sufficient anti-tumor response. However, achieving sustained levels of immune effector molecules and cells in the patient is difficult and generally requires large amounts of protein or cells to be administered over a prolonged period of time.Active vaccination refers to the process of stimulating the patient's own immune system to drive an anti-tumor response. The major attraction of this approach is the potential to generate immunological memory, which may protect against relapsing tumors. Preclinical breast cancer vaccine strategies targeting Her2/neu and other breast cancer antigens established the proof of principle of the approach [5,6]. Encouragingly, early-phase clinical studies using peptides derived from the Her2/neu protein (E75