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Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens

  1. Author:
    Whiteaker, Jeffrey R
    Lundeen, Rachel A
    Zhao, Lei
    Schoenherr, Regine M
    Burian, Aura
    Huang, Dongqing
    Voytovich, Ulianna
    Wang, Tao
    Kennedy, Jacob J
    Ivey, Richard G
    Lin, Chenwei
    Murillo, Oscar D
    Lorentzen, Travis D
    Thiagarajan,Mathangi
    Colantonio,Simona
    Caceres,Tessa
    Roberts,Rhonda
    Knotts,Joseph
    Reading,Joshua
    Kaczmarczyk,Jan
    Richardson, Christopher W
    Garcia-Buntley,Stephanie
    Bocik,William
    Hewitt, Stephen M
    Murray, Karen E
    Do, Nhan
    Brophy, Mary
    Wilz, Stephen W
    Yu, Hongbo
    Ajjarapu, Samuel
    Boja, Emily
    Hiltke, Tara
    Rodriguez, Henry
    Paulovich, Amanda G

  2. Author Address

    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States., Frederick National Laboratory for Cancer Research, Frederick, MD, United States., Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States., Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United States., Veteran 39;s Administration (VA) Cooperative Studies Program, Veteran 39;s Administration (VA) Boston Healthcare System (151MAV), Jamaica Plain, MA, United States., Department of Medicine, Boston University School of Medicine, Boston, MA, United States., Pathology and Laboratory Medicine Service, Program, Veteran 39;s Administration (VA) Boston Healthcare System, Jamaica Plain, MA, United States., Department of Pathology, Harvard Medical School, Boston, MA, United States., Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, United States., Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD, United States.,
    1. Year: 2021
    2. Date: Nov 11
  2. Journal: Frontiers in immunology
    1. 12
  4. Type of Article: Article
  5. Article Number: 765898
  6. ISSN: 1664-3224
  1. Abstract:

    Immunotherapies are revolutionizing cancer care, producing durable responses and potentially cures in a subset of patients. However, response rates are low for most tumors, grade 3/4 toxicities are not uncommon, and our current understanding of tumor immunobiology is incomplete. While hundreds of immunomodulatory proteins in the tumor microenvironment shape the anti-tumor response, few of them can be reliably quantified. To address this need, we developed a multiplex panel of targeted proteomic assays targeting 52 peptides representing 46 proteins using peptide immunoaffinity enrichment coupled to multiple reaction monitoring-mass spectrometry. We validated the assays in tissue and plasma matrices, where performance figures of merit showed over 3 orders of dynamic range and median inter-day CVs of 5.2% (tissue) and 21% (plasma). A feasibility study in clinical biospecimens showed detection of 48/52 peptides in frozen tissue and 38/52 peptides in plasma. The assays are publicly available as a resource for the research community. Copyright © 2021 Whiteaker, Lundeen, Zhao, Schoenherr, Burian, Huang, Voytovich, Wang, Kennedy, Ivey, Lin, Murillo, Lorentzen, Thiagarajan, Colantonio, Caceres, Roberts, Knotts, Reading, Kaczmarczyk, Richardson, Garcia-Buntley, Bocik, Hewitt, Murray, Do, Brophy, Wilz, Yu, Ajjarapu, Boja, Hiltke, Rodriguez and Paulovich.

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External Sources

  1. View Full Text
  2. DOI: 10.3389/fimmu.2021.765898
  3. PMID: 34858420
  4. PMCID: PMC8632241
  5. View record in Web of Science®
  6. WOS: 000726139800001

Library Notes

  1. Open Access Publication
  2. Fiscal Year: FY2021-2022
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