Frontiers in Oncology (May 2023)
A multiplexed assay for quantifying immunomodulatory proteins supports correlative studies in immunotherapy clinical trials
- Jeffrey R. Whiteaker,
- Lei Zhao,
- Regine M. Schoenherr,
- Dongqing Huang,
- Rachel A. Lundeen,
- Ulianna Voytovich,
- Jacob J. Kennedy,
- Richard G. Ivey,
- Chenwei Lin,
- Oscar D. Murillo,
- Travis D. Lorentzen,
- Simona Colantonio,
- Tessa W. Caceres,
- Rhonda R. Roberts,
- Joseph G. Knotts,
- Joshua J. Reading,
- Candice D. Perry,
- Christopher W. Richardson,
- Sandra S. Garcia-Buntley,
- William Bocik,
- Stephen M. Hewitt,
- Shrabanti Chowdhury,
- Jackie Vandermeer,
- Jackie Vandermeer,
- Stephen D. Smith,
- Stephen D. Smith,
- Ajay K. Gopal,
- Ajay K. Gopal,
- Nirasha Ramchurren,
- Steven P. Fling,
- Pei Wang,
- Amanda G. Paulovich
Affiliations
- Jeffrey R. Whiteaker
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Lei Zhao
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Regine M. Schoenherr
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Dongqing Huang
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Rachel A. Lundeen
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Ulianna Voytovich
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Jacob J. Kennedy
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Richard G. Ivey
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Chenwei Lin
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Oscar D. Murillo
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Travis D. Lorentzen
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Simona Colantonio
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Tessa W. Caceres
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Rhonda R. Roberts
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Joseph G. Knotts
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Joshua J. Reading
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Candice D. Perry
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Christopher W. Richardson
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Sandra S. Garcia-Buntley
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- William Bocik
- Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Stephen M. Hewitt
- Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United States
- Shrabanti Chowdhury
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Jackie Vandermeer
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Jackie Vandermeer
- Division of Medical Oncology, Department of Internal Medicine, University of Washington, Seattle, WA, United States
- Stephen D. Smith
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Stephen D. Smith
- Division of Medical Oncology, Department of Internal Medicine, University of Washington, Seattle, WA, United States
- Ajay K. Gopal
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Ajay K. Gopal
- Division of Medical Oncology, Department of Internal Medicine, University of Washington, Seattle, WA, United States
- Nirasha Ramchurren
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Steven P. Fling
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Pei Wang
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Amanda G. Paulovich
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- DOI
- https://doi.org/10.3389/fonc.2023.1168710
- Journal volume & issue
-
Vol. 13
Abstract
IntroductionImmunotherapy is an effective treatment for a subset of cancer patients, and expanding the benefits of immunotherapy to all cancer patients will require predictive biomarkers of response and immune-related adverse events (irAEs). To support correlative studies in immunotherapy clinical trials, we are developing highly validated assays for quantifying immunomodulatory proteins in human biospecimens.MethodsHere, we developed a panel of novel monoclonal antibodies and incorporated them into a novel, multiplexed, immuno-multiple reaction monitoring mass spectrometry (MRM-MS)-based proteomic assay targeting 49 proteotypic peptides representing 43 immunomodulatory proteins.Results and discussionThe multiplex assay was validated in human tissue and plasma matrices, where the linearity of quantification was >3 orders of magnitude with median interday CVs of 8.7% (tissue) and 10.1% (plasma). Proof-of-principle demonstration of the assay was conducted in plasma samples collected in clinical trials from lymphoma patients receiving an immune checkpoint inhibitor. We provide the assays and novel monoclonal antibodies as a publicly available resource for the biomedical community.
Keywords
