The present invention relates to methods and compositions of activating cytotoxic T lymphocytes (CTLs) in vivo with specificity for particular antigenic peptides, and to methods and compositions of using activated CTLs in vivo for the treatment of a variety of disease conditions. In some preferred embodiments, the invention provides methods of employing a polypeptide of the amino acid sequence VMAGVGSPYV to specifically activating CTLs in subjects having a breast cancer overexpressing a Her-2/Neu protein, and methods of using the polypeptide to treat such subjects.