Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants
Author(s)
Stopfer, Lauren E; Gajadhar, Aaron S; Patel, Bhavin; Gallien, Sebastien; Frederick, Dennie T; Boland, Genevieve M; Sullivan, Ryan J; White, Forest M; ... Show more Show less
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<jats:p>Absolute quantification measurements (copies per cell) of peptide major histocompatibility complex (pMHC) antigens are necessary to inform targeted immunotherapy drug design; however, existing methods for absolute quantification have critical limitations. Here, we present a platform termed SureQuant-IsoMHC, utilizing a series of pMHC isotopologues and internal standard-triggered targeted mass spectrometry to generate an embedded multipoint calibration curve to determine endogenous pMHC concentrations for a panel of 18 tumor antigens. We apply SureQuant-IsoMHC to measure changes in expression of our target panel in a melanoma cell line treated with a MEK inhibitor and translate this approach to estimate antigen concentrations in melanoma tumor biopsies.</jats:p>
Date issued
2021Department
Massachusetts Institute of Technology. Department of Biological EngineeringJournal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Citation
Stopfer, Lauren E, Gajadhar, Aaron S, Patel, Bhavin, Gallien, Sebastien, Frederick, Dennie T et al. 2021. "Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants." Proceedings of the National Academy of Sciences of the United States of America, 118 (37).
Version: Final published version