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Conférence CRCT : Dr Valérie Dutoit / Université de Genève – Therapeutic vaccination for glioblastoma
février 7 @ 11:00 - 12:00
The peptidome contains the critical peptides presented at the tumor cell surface having the potential to be recognized by CD8 T lymphocytes. We used peptide elution to identify 10 glioblastoma-associated HLA-A2-resscticted antigens that had the characteristics to be highly expressed in tumors, to have very low or absent expression in healthy tissues, and to be immunogenic. These peptides were formulated in the IMA950 multipeptide vaccine that was tested in a phase I/II study in combination with poly-ICLC in patients with newly diagnosed glioblastoma multiforme (n=16) and grade III astrocytoma (n=3, NCT01920191). Two MHC class II-binding peptides were added in order to generate an integrated T cell response. We observed that the IMA950/poly-ICLC vaccine was safe and well tolerated. For the first 6 patients, vaccine-induced CD8 T cell responses were restricted to a single peptide and CD4 responses were not detectable. After optimization of the vaccine formulation, we observed multipeptide CD8 and sustained Th1 CD4 T cell responses. For the entire cohort (n=19), CD8 T cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. An encouraging median overall survival of 21 months was obtained. These results prompted us to further test this vaccine in combination with an anti-PD1, comparing IMA950/poly-ICLC vs. IMA950/poly-ICLC+anti-PD1 in patients with recurrent GBM.