Glycoprotein tumor antigens for immunotherapy of breast cancer.

Continued progress in breast cancer immunotherapy, in particular breast cancer vaccines, depends on the identification of target molecules aberrantly expressed on breast cancer cells. Many different approaches to antigen discovery, including the recent developments in genomics and proteomics, have favored identification of protein tumor antigens. While some of these molecules provide important peptide epitopes recognized by T cells and antibodies, they represent only a small minority of potential targets. Considering that the majority of the cell proteins and therefore tumor cell proteins are glycosylated, tumor glycopeptides represent more important tumor-specific targets. Protein glycosylation is known to be dysregulated in cancer cells, leading to the accumulation of tumor-specific glycoproteins actively involved in tumor progression and metastasis. In addition to understanding the glycobiology of tumor cells and identifying tumor-specific glycoprotein antigens, better understanding is required of how the innate and the adaptive immune systems handle processing, presentation and recognition of glycoprotein antigens. We discuss here some of the new therapeutic strategies for exploiting abnormal glycosylation pathways in tumors and using defined carbohydrate and/or glycoprotein tumor antigens in active specific immunotherapy of breast cancer.