Vaccines in breast cancer

dSeveral antigens recognized by cellular and humoral effectors of the immun e 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, over expressed antigens, e.g. p53, HER2/neu, MUC-1, LewisX; and mutational antig ens, e.g. p53, represent potential targets for antigen-specific immunothera py. Clinical vaccine studies, mostly performed in melanoma, and aimed at th e 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 c losely correlate with the induction of antigen-specific CD8+ T cell respons es. Cytokines (GM-CSF, IL-2, IL-12) and adjuvants (QS21, IFA, MHC class II restricted helper peptides) have mediated increased CD8+ T cell responses a gainst different antigenic peptides. The site of immunization may have important implications for the quality of immune responses induced. Intradermal and intralymphatic vaccination has l ed to strong CD8+ T cell responses in vivo, measurable at the immunization site, in metastatic lesions and in the peripheral blood. Intravenous and su bcutaneous vaccination have induced measurable immune responses less freque ntly. Different strategies of vaccination using dendritic cells loaded with antigenic peptides. proteins or lysates prepared from autologous or alloge neic tumour cells have also led to measurable immune responses in vivo. Res ults, however. were not superior to vaccination with antigenic peptides alo ne or combined with adjuvants. Focusing on breast cancer, one of the most promising antigens for the desig n of vaccine studies is the CT-antigen NY-ESO-1. which was identified by th e SEREX method. NY-ESO-1 is expressed in approximately 30-50% of breast can cers. Spontaneous humoral and cellular immune responses against NY-ESO-1 ca n 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 p atients. Measurable immune responses that can be correlated with the clinic al outcome represent an important prerequisite for any immunotherapeutic in tervention in cancer immunotherapy. At present, measurable but limited dise ase will teach us about any immediate effects of immunotherapy on cancer ce lls. This will lead the way in the near future to sound and justified adjuv ant treatment strategies in the specific immunotherapy of breast cancer. (C ) 2001 Harcourt Publishers Ltd.