Tumor antigens and markers for breast and ovarian cancers

Use of vaccines to prevent and treat breast and ovarian cancer is a highly attractive approach because of the expected minimal side effects and the potential to predict individuals likely to benefit from vaccination. To fully harness the capacity of the immune system for this purpose, it is necessary to characterize tumor antigens for these cancers so that purified antigens can be tested for their immunogenicity in individual patients and for their suitability as targets of vaccine-induced immunity. Discovery of novel breast and ovarian tumor antigens is also necessary for developing multi-antigen vaccines composed of multiple tumor antigens. Such vaccines are expected to induce diverse immune responses and minimize emergence of antigen-loss variant tumors that are resistant to vaccine-induced immunity. With the exception of melanomas, for most human cancers including breast and ovarian cancers the repertoire of known tumor antigens remains relatively small. In this review we will discus the importance of characterizing tumor antigens for use in vaccination against cancer and then summarize antigens that have been characterized for human breast and ovarian cancers. We will also emphasize that identification of a novel tumor antigen, while an important first step, needs to be followed by a multi-step process of validation of that antigen. The steps in this validation process are i) to demonstrate that a tumor antigen is over-expressed at a reasonable frequency in primary tumors and in metastases; ii) to demonstrate the immunogenicity of a tumor antigen in an appropriate animal model; iii) to demonstrate its immunogenicity and safety in humans. Additional considerations in this review include: i) discussion of the potential of breast and ovarian tumor antigens as markers for early detection and for monitoring tumor burden in cancer patients; ii) discussion of their potential as prognostic markers of breast and ovarian cancers; and iii) discussion of a unique class of tumor antigens and markers that induce expression of multiple other tumor antigens and markers. Finally, we will discuss the present evidence for potential for autoimmunity that might accompany antitumor vaccination.