optiPRM: a targeted immunopeptidomics LC-MS workflow with ultra-high sensitivity for the detection of mutation-derived tumor neoepitopes from limited input material
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 muta...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
5 August 2024
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| In: |
Molecular & cellular proteomics
Year: 2024, Jahrgang: 23, Heft: 9, Pages: 1-16 |
| ISSN: | 1535-9484 |
| DOI: | 10.1016/j.mcpro.2024.100825 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.mcpro.2024.100825 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1535947624001154 
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| Verfasserangaben: | Mogjiborahman Salek, Jonas D. Förster, Jonas P. Becker, Marten Meyer, Pornpimol Charoentong, Yanhong Lyu, Katharina Lindner, Catharina Lotsch, Michael Volkmar, Frank Momburg, Isabel Poschke, Stefan Fröhling, Marc Schmitz, Rienk Offringa, Michael Platten, Dirk Jäger, Inka Zörnig, Angelika B. Riemer |
MARC
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| 520 | |a 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. | ||
| 650 | 4 | |a adoptive cell therapy (ACT) | |
| 650 | 4 | |a cancer vaccines | |
| 650 | 4 | |a human leukocyte antigen (HLA) | |
| 650 | 4 | |a immunopeptidomics | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a major histocompatibility complex (MHC) | |
| 650 | 4 | |a mutation | |
| 650 | 4 | |a neoantigen | |
| 650 | 4 | |a neoepitope | |
| 650 | 4 | |a normalized collision energy (NCE) | |
| 650 | 4 | |a parallel reaction monitoring (PRM) | |
| 650 | 4 | |a parameter optimization | |
| 650 | 4 | |a targeted mass spectrometry | |
| 650 | 4 | |a transgenic TCR (trTCR) | |
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