gms | German Medical Science

63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

13. - 16. Juni 2012, Leipzig

Development of a GBM vaccine based on HLA-A2-associated peptides

Meeting Abstract

  • C.H. Herold-Mende - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • V. Dutoit - Laboratory of Tumor Immunology, Oncology Department, Geneva University Hospital, Geneva, Switzerland
  • P. Beckhove - Translationale Immunologie, DKFZ Heidelberg
  • P.Y. Dietrich - Laboratory of Tumor Immunology, Oncology Department, Geneva University Hospital, Geneva, Switzerland
  • H.S. Singh-Jasuja - Immatics Biotechnologies GmbH, Tübingen
  • A. Unterberg - Sektion Neurochirurgische Forschung, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocSA.01.02

DOI: 10.3205/12dgnc300, URN: urn:nbn:de:0183-12dgnc3006

Veröffentlicht: 4. Juni 2012

© 2012 Herold-Mende et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Cancer vaccines are an attractive alternative to standard cancer treatments and are already being tested in humans. Ideally, T-cell-mediated tumor immunotherapy is directed against several tumor-associated antigens in order to circumvent the so called 'immune escape'.

Methods: To identify suitable peptides for vaccination therapy 32 HLA A2-positive GBM samples were submitted to peptide elution from MHC/peptide complexes using HPLC/MS, and the isolated peptides were sequenced followed by a comparative mRNA expression analysis of the same GBM samples and normal brain as well as non-CNS normal tissues. Expression of selected proteins was tested by immunohistochemistry using a tissue microarray including biopsies of 221 GBM and 29 recurrent tumors. In vitro immunogenicity of selected peptides was tested by using PBMCs of healthy individuals and GBM patients.

Results: More than three thousand A2-restricted peptides were isolated and analyzed according to comparative expression in GBM vs. normal brain and non-CNS tissues, resulting in the selection of 10 glioma-associated antigens. Interestingly, the set of peptides identified did not overlap with previously described glioma antigens. Importantly, there was no tolerance to the glioma antigens in GBM patients corroborating the relevance of the selected peptides. Finally, expression analysis in a large set of tumors revealed that corresponding proteins were present in 75–100% of primary and recurrent GBM analyzed. However, frequency of antigen-expressing tumor cells varied markedly with a mean of 14–88% positive cells which further supports the need that an effective anti-GBM vaccine should be directed against several tumor-associated proteins to target as many tumor cells as possible.

Conclusions: The originality and power of this approach has allowed to fill a gap in the field of glioma immunotherapy by identifying novel glioma-associated antigens. The antigens we have isolated meet the criteria of overexpression in tumor samples versus normal tissues and were incorporated into the multipeptide vaccine IMA950 which will now be tested for the treatment of GBM and recurrent GBM in three independent clinical phase I trials.