title: Application of protein microarrays for multiplexed detection of antibodies to tumor antigens in breast cancer.
abstract: There is strong preclinical evidence that cancer, including breast cancer, undergoes immune surveillance. This continual monitoring, by both the innate and the adaptive immune systems, recognizes changes in protein expression, mutation, folding, glycosylation, and degradation. Local immune responses to tumor antigens are amplified in draining lymph nodes, and then enter the systemic circulation. The antibody response to tumor antigens, such as p53 protein, are robust, stable, and easily detected in serum; may exist in greater concentrations than their cognate antigens; and are potential highly specific biomarkers for cancer. However, antibodies have limited sensitivities as single analytes, and differences in protein purification and assay characteristics have limited their clinical application. For example, p53 autoantibodies in the sera are highly specific for cancer patients, but are only detected in the sera of 10-20% of patients with breast cancer. Detection of p53 autoantibodies is dependent on tumor burden, p53 mutation, rapidly decreases with effective therapy, but is relatively independent of breast cancer subtype. Although antibodies to hundreds of other tumor antigens have been identified in the sera of breast cancer patients, very little is known about the specificity and clinical impact of the antibody immune repertoire to breast cancer. Recent advances in proteomic technologies have the potential for rapid identification of immune response signatures for breast cancer diagnosis and monitoring. We have adapted programmable protein microarrays for the specific detection of autoantibodies in breast cancer. Here, we present the first demonstration of the application of programmable protein microarray ELISAs for the rapid identification of breast cancer autoantibodies.
authors.affiliation: Cancer Vaccine Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Niroshan
authors.initials: N
authors.lastname: Ramachandran
authors.forename: Jessica
authors.initials: J
authors.lastname: Wong
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Raphael
authors.forename: Eugenie
authors.initials: E
authors.lastname: Hainsworth
authors.forename: Gokhan
authors.initials: G
authors.lastname: Demirkan
authors.forename: Daniel
authors.initials: D
authors.lastname: Cramer
authors.forename: Dina
authors.initials: D
authors.lastname: Aronzon
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Harris
authors.forename: Tanya
authors.initials: T
authors.lastname: Logvinenko
authors.forename: Joshua
authors.initials: J
authors.lastname: LaBaer
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; C107489:BIRC5 protein, human; D015415:Biomarkers; D018985:Epitopes, B-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C417029:EBV-encoded nuclear antigen 1