Back to Search
Start Over
Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy.
- Source :
- Brain: A Journal of Neurology; Apr2012, Vol. 135 Issue 4, p1042-1054, 13p
- Publication Year :
- 2012
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00068950
- Volume :
- 135
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Brain: A Journal of Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 74495930
- Full Text :
- https://doi.org/10.1093/brain/aws042