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optiPRM: A Targeted Immunopeptidomics LC-MS Workflow With Ultra-High Sensitivity for the Detection of Mutation-Derived Tumor Neoepitopes From Limited Input Material.
Salek, Mogjiborahman; Förster, Jonas D; Becker, Jonas P; Meyer, Marten; Charoentong, Pornpimol; Lyu, Yanhong; Lindner, Katharina; Lotsch, Catharina; Volkmar, Michael; Momburg, Frank; Poschke, Isabel; Fröhling, Stefan; Schmitz, Marc; Offringa, Rienk; Platten, Michael; Jäger, Dirk; Zörnig, Inka; Riemer, Angelika B.
Afiliación
  • Salek M; Division of Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Molecular Vaccine Design, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany.
  • Förster JD; Division of Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Molecular Vaccine Design, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, German
  • Becker JP; Division of Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Molecular Vaccine Design, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany.
  • Meyer M; Antigen Presentation and T/NK Cell Activation Group, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Department of Medical Oncology, National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany.
  • Charoentong P; Department of Medical Oncology, National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Center
  • Lyu Y; Department of Medical Oncology, National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany.
  • Lindner K; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Immune Monitoring Unit, National Center for Tumor Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Hei
  • Lotsch C; Division of Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Molecular Vaccine Design, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, German
  • Volkmar M; T Cell Discovery Platform, Helmholtz Institute for Translational Oncology (HI-TRON) Mainz - A Helmholtz Institute of the DKFZ, Mainz, Germany.
  • Momburg F; Antigen Presentation and T/NK Cell Activation Group, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
  • Poschke I; Immune Monitoring Unit, National Center for Tumor Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuroimmunology and Brai
  • Fröhling S; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany; Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT), NCT Heidelberg,
  • Schmitz M; Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), NCT Dresden, A PARTNership between DKFZ, University Hospital Carl Gustav Carus, Faculty of Medicine Carl Gustav Carus of TU Dresden and Helmholtz Center Dresden-Ros
  • Offringa R; Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
  • Platten M; Immune Monitoring Unit, National Center for Tumor Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuroimmunology and Brai
  • Jäger D; Department of Medical Oncology, National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
  • Zörnig I; Department of Medical Oncology, National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
  • Riemer AB; Division of Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany; Molecular Vaccine Design, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany. Electronic address: a.riemer@dkfz.de.
Mol Cell Proteomics ; 23(9): 100825, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39111711
ABSTRACT
Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteómica / Flujo de Trabajo / Mutación Límite: Animals / Humans Idioma: En Revista: Mol Cell Proteomics Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteómica / Flujo de Trabajo / Mutación Límite: Animals / Humans Idioma: En Revista: Mol Cell Proteomics Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos