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

Brain. 2012 Apr;135(Pt 4):1042-54. doi: 10.1093/brain/aws042. Epub 2012 Mar 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / physiology
  • Antigens, CD / metabolism
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / therapeutic use
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • CD8-Positive T-Lymphocytes / immunology
  • Chromatography, Liquid
  • Cytokines / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioblastoma / immunology*
  • Glioblastoma / pathology
  • Glioblastoma / therapy
  • HLA-A Antigens / analysis
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / immunology
  • Humans
  • Mass Spectrometry
  • Oligonucleotide Array Sequence Analysis
  • Peptides / analysis
  • Peptides / immunology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • RNA, Messenger / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Sequence Analysis, Protein


  • Antigens, CD
  • Antigens, Neoplasm
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • HLA-A Antigens
  • Peptides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • PTPRZ1 protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5