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.