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

被引:36
作者
Dutoit, Valerie [1 ,2 ]
Migliorini, Denis [1 ,2 ]
Ranzanici, Giulia [1 ,2 ]
Marinari, Eliana [1 ,2 ]
Widmer, Valerie [1 ,2 ]
Lobrinus, Johannes Alexander [3 ,4 ]
Momjian, Shahan [4 ,5 ]
Costello, Joseph [6 ]
Walker, Paul R. [1 ,2 ]
Okada, Hideho [6 ,7 ,8 ]
Weinschenk, Toni [9 ]
Herold-Mende, Christel [10 ]
Dietrich, Pierre-Yves [1 ,2 ]
机构
[1] Geneva Univ Hosp, Dept Oncol, Rue Gabrielle Perret Gentil 4, CH-1204 Geneva 11, Switzerland
[2] Univ Geneva, Dept Internal Med Specialties, Fac Med, Rue Michel Servet 1, CH-1205 Geneva, Switzerland
[3] Geneva Univ Hosp, Div Clin Pathol, Rue Gabrielle Perret Gentil 4, CH-1204 Geneva 11, Switzerland
[4] Univ Geneva, Rue Gabrielle Perret Gentil 4, CH-1204 Geneva 11, Switzerland
[5] Geneva Univ Hosp, Neurosurg Serv, Rue Gabrielle Perret Gentil 4, CH-1204 Geneva 11, Switzerland
[6] Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, 505 Parnassus Ave,Room 779 M, San Francisco, CA USA
[7] Univ Calif San Francisco, Canc Immunotherapy Program, 1 Letterman Dr,Suite D3500, San Francisco, CA 94143 USA
[8] Parker Inst Canc Immunotherapy, 1 Letterman Dr,Suite D3500, San Francisco, CA USA
[9] Immat Biotechnol GmbH, Paul Ehrlich Str 15, Tubingen, Germany
[10] Heidelberg Univ, Div Expt Neurosurg, Dept Neurosurg, Neuenheimer Feld 400, Heidelberg, Germany
关键词
grade II glioma; grade III glioma; immunotherapy; peptide vaccine; IMA950; spontaneous T cell responses; astrocytoma; oligodendroglioma; ependymoma; T-CELLS; ANTITUMOR IMMUNITY; POLY-ICLC; IDENTIFICATION; TUMOR; EPENDYMOMA; IDH1; PROGRESSION; LYMPHOCYTES; STRATEGIES;
D O I
10.1080/2162402X.2017.1391972
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:10
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