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Single-Molecule Arrays for Ultrasensitive Detection of Blood-Based Biomarkers for Immunotherapy

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Biomarkers for Immunotherapy of Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2055))

Abstract

Single-molecule array (Simoa) technology enables ultrasensitive protein detection that is suited to the development of peripheral blood-based assays for assessing immuno-oncology responses. We adapted a panel of Simoa assays to measure systemic cytokine levels from plasma and characterized physiologic variation in healthy individuals and preanalytic variation arising from processing and handling of patient samples. Insights from these preclinical studies led us to a well-defined set of Simoa assay conditions, a specimen processing protocol, and a data processing approach that we describe here. Simoa enables accurate quantitation of soluble immune signaling molecules in an unprecedented femtomolar range, opening up the potential for liquid biopsy-type approaches in immuno-oncology. We are using the method described here to distinguish PD-1 inhibitor nonresponders as early as after one dose after therapy and envision applications in characterizing PD-1 inhibitor resistance and detection of immune-related adverse effects.

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Acknowledgments

L.C. and D.R.W. were funded by DARPA (HR0011-12-2-0001; Pass-through-entity: Univ. of North Carolina Chapel-Hill, subaward 5055065).

Conflict of Interest: The authors declare the following competing financial interest: David R. Walt is the scientific founder and a board member of Quanterix Corporation. All other authors declare no competing financial interest.

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Limor Cohen, Alissa Keegan & David R. Walt

  2. Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA

    Limor Cohen & David R. Walt

  3. Department of Chemical Biology, Harvard University, Boston, MA, USA

    Limor Cohen

Authors
  1. Limor Cohen
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  2. Alissa Keegan
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  3. David R. Walt
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Corresponding author

Correspondence to Alissa Keegan .

Editor information

Editors and Affiliations

  1. NIH, National Cancer Institute, Bethesda, MD, USA

    Magdalena Thurin

  2. Nanostring Technologies, Seattle, WA, USA, ESSA Pharma, South San Francisco, CA, USA

    Alessandra Cesano

  3. Refuge Biotechnologies, Menlo Park, CA, USA

    Francesco M. Marincola

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Cohen, L., Keegan, A., Walt, D.R. (2020). Single-Molecule Arrays for Ultrasensitive Detection of Blood-Based Biomarkers for Immunotherapy. In: Thurin, M., Cesano, A., Marincola, F. (eds) Biomarkers for Immunotherapy of Cancer. Methods in Molecular Biology, vol 2055. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9773-2_18

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  • DOI: https://doi.org/10.1007/978-1-4939-9773-2_18

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9772-5

  • Online ISBN: 978-1-4939-9773-2

  • eBook Packages: Springer Protocols

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