Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology

Weidanz, Jon A.; Doll, Krysten L.; Mohanasundaram, S.; Wichner, Timea; Lowe, Devin B.; Gimlin, Susanne; Weidanz, Debra Wawro; Magnusson, Robert; Hawkins, Oriana E.

doi:10.3791/52159

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…This led to the investigation of peptides eluted from soluble HLA (sHLA) complexes, recovered from the blood of patients with hematological malignancies, such as multiple myeloma, acute lymphoblastic leukemia or acute myeloid leukemia [21]. Furthermore, soluble HLA molecules complexed with disease-associated epitopes found in the blood of breast cancer patients were proposed to serve as possible biomarkers and companion diagnostics [22].…”

Section: Introductionmentioning

confidence: 99%

High‐sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients’ sera

et al. 2016

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The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high-confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan-reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

High‐sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients’ sera

et al. 2016

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“…The above-mentioned study by Bassani-Stenberg ( 33 ) identified a number of peptides derived from cancer-testis antigens (CTA) and tumor-associated antigens (TAA) in the blood of patients with hematological malignancies. More recent studies observed that sHLA complexes containing peptides derived from validated CTAs (macrophage inhibitory factor ( 49 , 50 ) & NY-ESO-1 ( 51 )) can be detected in the blood of breast cancer patients ( 52 ).…”

Section: Sourcing Biomarkers From Soluble Hla: Current Evidence and E...mentioning

confidence: 99%

Soluble HLA peptidome: A new resource for cancer biomarkers

2022

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Using circulating molecular biomarkers to screen for cancer and other debilitating disorders in a high-throughput and low-cost fashion is becoming increasingly attractive in medicine. One major limitation of investigating protein biomarkers in body fluids is that only one-fourth of the entire proteome can be routinely detected in these fluids. In contrast, Human Leukocyte Antigen (HLA) presents peptides from the entire proteome on the cell surface. While peptide-HLA complexes are predominantly membrane-bound, a fraction of HLA molecules is released into body fluids which is referred to as soluble HLAs (sHLAs). As such peptides bound by sHLA molecules represent the entire proteome of their cells/tissues of origin and more importantly, recent advances in mass spectrometry-based technologies have allowed for accurate determination of these peptides. In this perspective, we discuss the current understanding of sHLA-peptide complexes in the context of cancer, and their potential as a novel, relatively untapped repertoire for cancer biomarkers. We also review the currently available tools to detect and quantify these circulating biomarkers, and we discuss the challenges and future perspectives of implementing sHLA biomarkers in a clinical setting.

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“…[4][5][6][7] Recent years, optical detection methods based on the effect of guided-mode resonance are often used in biological testing. For example, optical devices combined with micro-nano structures based on this theory have been used in cancer detection, 8,9 serum concentrations of human IgE antibodies detection, 10 and live cell adhesion imaging.…”

Section: Introductionmentioning

confidence: 99%

Portable organic gas detection sensor based on the effect of guided-mode resonance

et al. 2017

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A novel organic gas detection sensor based on the effect of guided-mode resonance is proposed in this paper. The sensor is designed to operate in the visible light band. It contains four main sections: a light source, a miniature gas chamber composed of a guided-mode resonant filter, a diffraction grating, and a CCD image sensor. When bunched visible light is irradiated vertically to the gas chamber, it passes through the gas chamber and diffraction grating, and is then received by the CCD sensor. The optical signal received by the CCD sensor is then reduced to the spectrum using a specific algorithm. When organic gases are injected into the gas chamber, there is a shift in the wavelength of resonant reflection, and the magnitude of this shift is proportional to the refractive index of the gas. The large variation in the refractive indexes of industrially important organic gases means that their characteristic peak wavelengths can be easily identified. As a result, this system can quickly detect organic gases. To verify the feasibility of this technique, we use finite difference time domain solutions to simulate the results. The sensitivity of this type of sensor can reach wavelength differences of 0.001 nm, which means that the sensor has high potential for application in portable, high-precision detection systems.

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Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology

Cited by 4 publications

References 14 publications

High‐sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients’ sera

High‐sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients’ sera

Soluble HLA peptidome: A new resource for cancer biomarkers

Portable organic gas detection sensor based on the effect of guided-mode resonance

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