Tumor-derived chaperone-rich cell lysate (CRCL), containing numerous heat shock proteins, has successfully been used to generate tumor-specific T cell responses against murine and human tumors. Here we report that tumor derived CRCL is able to elicit humoral immune responses against HER-2/neu, which is over-expressedin several human tumors including breast cancer. The selective expression of HER-2/neu and its role in epithelial carcinogenesis makes HER-2/neu an ideal target for immunotherapy. The therapeutic potential and mechanism of CRCL vaccine derived from HER-2/neu specific tumor was examinedusing a transplantablemouse tumor model. Vaccination of mice bearing palpable tumor efficiently delayed tumor growth. Evaluation of the immune responses during CRCL vaccination demonstrated significant anti-HER2/neu antibody production. The functional significance of HER-2/neu specific antibodies was tested with serum transfer into SCID mice and vaccination of B cell deficient mice. These studies demonstrated that the induction ofanti-HER2/neu antibodies is both necessary and sufficient for tumor growth suppression. Additionally we have studied the mechanisms of antibody-mediated protection in several ways, including antibody dependent cellular cytotoxicity and down-regulation of HER-2/neu molecules from the surface of the tumor cells. These are significant observations since not much is known about the mechanism of the humoral responses induced by HSP-derived vaccines. These results indicate that CRCL this personalized vaccine may be a promising approach of active immunotherapy for women suffering from HER2/neu positive breast cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA