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Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

Dutoit, Valérie ; Herold-Mende, Christel ; Hilf, Norbert ; Schoor, Oliver ; Beckhove, Philipp ; Bucher, Judith ; Dorsch, Katharina ; Flohr, Sylvia ; Fritsche, Jens ; Lewandrowski, Peter ; Lohr, Jennifer ; Rammensee, Hans-Georg ; Stevanovic, Stefan ; Trautwein, Claudia ; Vass, Verona ; Walter, Steffen ; Walker, Paul R. ; Weinschenk, Toni ; Singh-Jasuja, Harpreet ; Dietrich, Pierre-Yves

In: Brain, 2012, vol. 135, no. 4, p. 1042-1054

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    Titre
    • Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy
    Auteur
    • Dutoit, Valérie. 1 Laboratory of Tumour Immunology, Centre of Oncology, University of Geneva and Geneva University Hospitals, 1211 Geneva 14, Switzerland
    • Herold-Mende, Christel. 2 Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany
    • Hilf, Norbert. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Schoor, Oliver. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Beckhove, Philipp. 4 Translational Immunology Unit, the German Cancer Research Centre, 69120 Heidelberg, Germany
    • Bucher, Judith. 2 Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany
    • Dorsch, Katharina. 2 Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany
    • Flohr, Sylvia. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Fritsche, Jens. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Lewandrowski, Peter. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Lohr, Jennifer. 2 Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany
    • Rammensee, Hans-Georg. 5 Department of Immunology, Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany
    • Stevanovic, Stefan. 5 Department of Immunology, Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany
    • Trautwein, Claudia. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Vass, Verona. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Walter, Steffen. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Walker, Paul R.. 1 Laboratory of Tumour Immunology, Centre of Oncology, University of Geneva and Geneva University Hospitals, 1211 Geneva 14, Switzerland
    • Weinschenk, Toni. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Singh-Jasuja, Harpreet. 3 Immatics Biotechnologies GmbH, 72076 Tübingen, Germany
    • Dietrich, Pierre-Yves. 1 Laboratory of Tumour Immunology, Centre of Oncology, University of Geneva and Geneva University Hospitals, 1211 Geneva 14, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Brain, 2012, vol. 135, no. 4, p. 1042-1054. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:304812
    Summary
    Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02+ glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8+ T cells in vitro. In vivo, glioblastoma-specific CD8+ T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma