Following these trials, further improvementof immunogenicity was achieved by linearly linking the peptides togive P467, and this peptide was coupled either to virosomes or todiphtheria toxoid CRM197, which, along with adjuvant, was used asa metastatic breast cancer vaccine.315 Thismultiepitope vaccine induced polyclonal antibodies with anti-proliferativeactivity against HER-2/neu, and on the basis of these promising findings,phase II trials were launched. This evidence concerns the gene ERBB2 and breast cancer.