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National Institute of Environmental Health Sciences

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Publication Detail

Title: Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants.

Authors: Stopfer, Lauren E; Gajadhar, Aaron S; Patel, Bhavin; Gallien, Sebastien; Frederick, Dennie T; Boland, Genevieve M; Sullivan, Ryan J; White, Forest M

Published In Proc Natl Acad Sci U S A, (2021 09 14)

Abstract: 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.

PubMed ID: 34497125 Exiting the NIEHS site

MeSH Terms: Antigen Presentation/drug effects; Antigen Presentation/immunology*; Antigens, Neoplasm/analysis*; Antigens, Neoplasm/drug effects; Antigens, Neoplasm/immunology; Benzimidazoles/pharmacology*; Histocompatibility Antigens Class I/immunology*; Histocompatibility Antigens Class I/metabolism; Humans; Immunotherapy; MAP Kinase Kinase 1/antagonists & inhibitors*; Melanoma/drug therapy; Melanoma/immunology*; Melanoma/metabolism; Tumor Cells, Cultured

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