Vaccines in breast cancer (2001)

Several antigens recognized by cellular and humoral effectors of the immune system have been identified in breast cancer. ‘Cancer/Testis’ antigens, e.g. MAGE, NY-ESO-1, CT-7; differentiation antigens, e.g. NY-BR-1, CEA; overexpressed antigens, e.g. p53, HER2/neu, MUC-1, LewisX; and mutational antigens, e.g. p53, represent potential targets for antigen-specific immunotherapy. Clinical vaccine studies, mostly performed in melanoma, and aimed at the induction of antigen-specific CD8+ T cell responses in vivo, have helped to establish sensitive tools for the monitoring of immune responses to the vaccine in vivo and in vitro. Delayed-type hypersensitivity (DTH) reactions observed after intradermal injection of antigenic peptides were found to closely correlate with the induction of antigen-specific CD8+ T cell responses. Cytokines (GM-CSF, IL-2, IL-12) and adjuvants (QS21, IFA, MHC class II restricted helper peptides) have mediated increased CD8+ T cell responses against different antigenic peptides. The site of immunization may have important implications for the quality of immune responses induced. Intradermal and intralymphatic vaccination has led to strong CD8+ T cell responses in vivo, measurable at the immunization site, in metastatic lesions and in the peripheral blood. Intravenous and subcutaneous vaccination have induced measurable immune responses less frequently. Different strategies of vaccination using dendritic cells loaded with antigenic peptides, proteins or lysates prepared from autologous or allogeneic tumour cells have also led to measurable immune responses in vivo. Results, however, were not superior to vaccination with antigenic peptides alone or combined with adjuvants. Focusing on breast cancer, one of the most promising antigens for the design of vaccine studies is the CT-antigen NY-ESO-1, which was identified by the SEREX method. NY-ESO-1 is expressed in approximately 30–50% of breast cancers. Spontaneous humoral and cellular immune responses against NY-ESO-1 can be detected in 50% of patients with NY-ESO-1+ tumours. Specific DTH- and CD8+ T cell responses were induced after vaccination with NY-ESO-1 derived peptides alone and combined with GM-CSF in the majority of NY-ESO-1-naive patients. Measurable immune responses that can be correlated with the clinical outcome represent an important prerequisite for any immunotherapeutic intervention in cancer immunotherapy. At present, measurable but limited disease will teach us about any immediate effects of immunotherapy on cancer cells. This will lead the way in the near future to sound and justified adjuvant treatment strategies in the specific immunotherapy of breast cancer. Several antigens recognized by cellular and humoral effectors of the immune system have been identified in breast cancer. ‘Cancer/Testis’ antigens, e.g. MAGE, NY-ESO-1, CT-7; differentiation antigens, e.g. NY-BR-1, CEA; overexpressed antigens, e.g. p53, HER2/neu, MUC-1, LewisX; and mutational antigens, e.g. p53, represent potential targets for antigen-specific immunotherapy. Clinical vaccine studies, mostly performed in melanoma, and aimed at the induction of antigen-specific CD8+ T cell responses in vivo, have helped to establish sensitive tools for the monitoring of immune responses to the vaccine in vivo and in vitro. Delayed-type hypersensitivity (DTH) reactions observed after intradermal injection of antigenic peptides were found to closely correlate with the induction of antigen-specific CD8+ T cell responses. Cytokines (GM-CSF, IL-2, IL-12) and adjuvants (QS21, IFA, MHC class II restricted helper peptides) have mediated increased CD8+ T cell responses against different antigenic peptides. The site of immunization may have important implications for the quality of immune responses induced. Intradermal and intralymphatic vaccination has led to strong CD8+ T cell responses in vivo, measurable at the immunization site, in metastatic lesions and in the peripheral blood. Intravenous and subcutaneous vaccination have induced measurable immune responses less frequently. Different strategies of vaccination using dendritic cells loaded with antigenic peptides, proteins or lysates prepared from autologous or allogeneic tumour cells have also led to measurable immune responses in vivo. Results, however, were not superior to vaccination with antigenic peptides alone or combined with adjuvants. Focusing on breast cancer, one of the most promising antigens for the design of vaccine studies is the CT-antigen NY-ESO-1, which was identified by the SEREX method. NY-ESO-1 is expressed in approximately 30–50% of breast cancers. Spontaneous humoral and cellular immune responses against NY-ESO-1 can be detected in 50% of patients with NY-ESO-1+ tumours. Specific DTH- and CD8+ T cell responses were induced after vaccination with NY-ESO-1 derived peptides alone and combined with GM-CSF in the majority of NY-ESO-1-naive patients. Measurable immune responses that can be correlated with the clinical outcome represent an important prerequisite for any immunotherapeutic intervention in cancer immunotherapy. At present, measurable but limited disease will teach us about any immediate effects of immunotherapy on cancer cells. This will lead the way in the near future to sound and justified adjuvant treatment strategies in the specific immunotherapy of breast cancer.