title: Detection of human leukocyte antigen biomarkers in breast cancer utilizing label-free biosensor technology.
abstract: According to the American Cancer Society, more than 200,000 women will be diagnosed with invasive breast cancer each year and approximately 40,000 will die from the disease. The human leukocyte antigen (HLA) class I samples peptides derived from proteasomal degradation of cellular proteins and presents these fragments on the cell surface for interrogation by circulating cytotoxic T lymphocytes (CTL). Generation of T-cell receptor mimic (TCRm) monoclonal antibodies (mAbs) which recognize breast cancer specific peptide/HLA-A*02:01 complexes such as those derived from macrophage migration inhibitory factor (MIF19-27) and NY-ESO-1157-165 enable detection and destruction of breast cancer cells in the absence of an effective anti-tumor CTL response. Intact class I HLA/peptide complexes are shed by breast cancer cells and represent potentially relevant cancer biomarkers. In this work, a breakthrough biomarker screening system for cancer diagnostics incorporating T-cell receptor mimic monoclonal antibodies combined with a novel, label-free biosensor utilizing guided-mode resonance (GMR) sensor technology is presented. Detection of shed MIF/HLA-A*02:01 complexes in MDA-MB-231 cell supernatants, spiked human serum, and patient plasma is demonstrated. The impact of this work could revolutionize personalized medicine through development of companion disease diagnostics for targeted immunotherapies.
authors: Experimmune, A Center for Immunotherapeutic Development, Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center.
authors: Jon A
authors: JA
authors: Weidanz
authors: Experimmune, A Center for Immunotherapeutic Development, Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center.
authors: Krysten L
authors: KL
authors: Doll
authors: Experimmune, A Center for Immunotherapeutic Development, Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center.
authors: Soumya
authors: S
authors: Mohana-Sundaram
authors: Experimmune, A Center for Immunotherapeutic Development, Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center.
authors: Timea
authors: T
authors: Wichner
authors: Experimmune, A Center for Immunotherapeutic Development, Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center.
authors: Devin B
authors: DB
authors: Lowe
authors: Resonant Sensors Incorporated.
authors: Susanne
authors: S
authors: Gimlin
authors: Resonant Sensors Incorporated.
authors: Debra
authors: D
authors: Wawro Weidanz
authors: Resonant Sensors Incorporated; University of Texas Arlington.
authors: Robert
authors: R
authors: Magnusson
authors: Experimmune, A Center for Immunotherapeutic Development, Department of Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center; oriana.hawkins@ttuhsc.edu.
authors: Oriana E
authors: OE
authors: Hawkins
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D015374:Biosensing Techniques / Q000379:methods*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015789:HLA-A2 Antigen / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000737:chemistry / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008263:Macrophage Migration-Inhibitory Factors; D010446:Peptide Fragments; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human