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Abstract Book 2010 - CIMT Annual Meeting

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L119 Dutoit | Therapeutic vaccination<br />

Functional immune reactivity to antigens of the novel<br />

IMA950 vaccine peptide set in glioma patients<br />

Valérie Dutoit 1 , Norbert Hilf 2 , Steffen Walter 2 , Toni Weinschenk 2 , Philippe Beckhove 3 , Christel<br />

Herold-Mende 4 , Paul Walker 1 , Harpreet Singh 2 and Pierre-Yves Dietrich 1<br />

1 Laboratory of tumor immunology, Oncology department, Geneva University Hospital, Geneva, Switzerland<br />

2 immatics biotechnologies GmbH, Tuebingen, Germany<br />

3 Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany<br />

4 Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Germany<br />

We have recently identified a new set of HLA-A2restricted<br />

glioma antigens isolated by direct elution<br />

from tumor cells for use in glioma immunotherapy.<br />

These antigens were selected from a large panel<br />

of eluted peptides according to overexpression in<br />

glioma compared to normal brain and other tissues,<br />

and relevance in tumorigenesis. In vitro peptide<br />

immunogenicity was investigated in healthy individuals,<br />

guiding the final vaccine peptide composition.<br />

Here, in order to validate the use of the novel peptide<br />

set for multipeptide vaccination, T cell reactivity<br />

and absence of tolerance was investigated in patients<br />

with malignant glioma. In addition, peptidespecific<br />

T cell function was assessed in vitro. All<br />

patients responded to several glioma peptides, suggesting<br />

that this multipeptide vaccine may benefit<br />

the majority of HLA-A2+ patients. Moreover,<br />

glioma peptide-specific CD8+ T cell clones generated<br />

from the blood of glioma patients were able to<br />

efficiently kill antigen-expressing tumor cells, but<br />

not K562 cells. Finally, CD8+ T cells specific for a<br />

brevican epitope were detected at the tumor site in<br />

one patient, showing that, for this antigen, spontaneously<br />

elicited specific T cells are retained at the<br />

tumor site. Altogether, our results validate the use<br />

of the ten novel glioma antigens in multipeptide<br />

vaccination and adoptive cell therapies for patients<br />

with glioma.<br />

57

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