Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma

Article Article scientifique Article Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma eng 2018 author Dutoit Vallotton Valérie 0000-0002-3469-4237 668630 author Migliorini Denis 838158 author Ranzanici Giulia Gabriella 635242 author Marinari Eliana 841772 author Widmer-Schnuriger Valérie 39000 author Lobrinus Johannes Alexander 647649 author Momjian Shahan Marc 84022 author Costello Joseph author Walker Paul Richard 0000-0001-8999-6366 104900 author Okada Hideho author Weinschenk Toni author Herold-Mende Christel author Dietrich Pierre-Yves 96532 e1391972 10.1080/2162402X.2017.1391972 29308320 2162-4011 Gliomas are lethal brain tumors that resist standard therapeutic approaches. Immunotherapy is a promising alternative strategy mostly developed in the context of glioblastoma. However, there is a need for implementing immunotherapy for grade II/III gliomas, as these are the most common CNS tumors in young adults with a high propensity for recurrence, making them lethal despite current treatments. We recently identified HLA-A2-restricted tumor-associated antigens by peptide elution from glioblastoma and formulated a multipeptide vaccine (IMA950) evaluated in phase I/II clinical trials with promising results. Here, we investigated expression of the IMA950 antigens in patients with grade II/III astrocytoma, oligodendroglioma or ependymoma, at the mRNA, protein and peptide levels. We report that the BCAN, CSPG4, IGF2BP3, PTPRZ1 and TNC proteins are significantly over-expressed at the mRNA (n = 159) and protein (n = 36) levels in grade II/III glioma patients as compared to non-tumor samples (IGF2BP3 being absent from oligodendroglioma). Most importantly, we detected spontaneous antigen-specific T cell responses to one or more of the IMA950 antigens in 100% and 71% of grade II and grade III patients, respectively (27 patients tested). These patients displayed T cell responses of better quality (higher frequency, broader epitope targeting) than patients with glioblastoma. Detection of spontaneous T cell responses to the IMA950 antigens shows that these antigens are relevant for tumor targeting, which will be best achieved by combination with CD4 epitopes such as the IDH1R132H peptide. Altogether, we provide the rationale for using a selective set of IMA950 peptides for vaccination of patients with grade II/III glioma. Dewey 616 Dewey 616.8 56 Département de médecine 221 61 Département des neurosciences cliniques 226 false 401 Immunobiologie des tumeurs du cerveau 669 27 Immunothérapie des cancers 42 OncoImmunology 7 2 860d099c-2bf7-4c0b-926c-51e93f2f4e14 Article (Published version) Public article.pdf 1137248 application/pdf CC BY-NC-ND openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

Title	Published in	Year	Views	Downloads

Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma	OncoImmunology	2018	671	433
Caractérisation d'antigènes pour la vaccinothérapie des gliomes de grade II et III		2016	680	0

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Ranzanici, Giulia Gabriella