The natural development of B cell antibody responses to tumor antigens is dependent on antigen overexpression, mutation, apoptosis, changes structural, and aberrant glycosylation (27). Aberrently glycosylated carbohydrate antigens, such as Tn, are expressed by tumor cells and have been used in clinical vaccine trials in breast cancer (28-31) with evidence of immunogenicity. Serologic expression cloning has been used to detect antibodies to multiple breast cancer protein antigens, including HER2/neu, p53, MUC1, and NY-ESO-1 (32-35). In prostate cancer, patterns of autoantibody production correlate with disease outcome (36), suggesting that autoantibodies may be useful as proteomic biomarkers both for diagnosis and prognosis (27). Similarly, antibodies to HER2/neu have been detected in serum samples from 20% of patients with HER2+ early-stage of breast cancer (32). Although HER2 antibody titers of exceeding 1:5000 have been reported, it is unclear whether they confer a protective immune response. Since B-cell immunity often correlates with T-cell immunity, autoantigen identification has led to the identification of T-cell antigens for vaccine development (37,38). Since tumor antigen-specific antibodies can enhance tumor antigen cross-presentation, combined vaccine and antibody therapy, such as HER2-vaccines and trastuzumab, may augment anti-tumor immunity.
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