Journal
ESMO OPEN
Volume 6, Issue 4, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.esmoop.2021.100214
Keywords
glioma; isocitrate dehydrogenase; neoantigen; vaccine; immunotherapy
Categories
Funding
- Dr Rolf M. Schwiete Foundation
- Sonderforderlinie 'Neuroinflammation' of the Ministry of Science of Baden Wurttemberg
- Joint Funding Program MGH-Heidelberg Alliance in Neuro-Oncology
- Wilhelm Sander Foundation [2012.118.1]
- NCT 3.0 program 'Cancer immunotherapy program' program 'genetically modified cells for cancer immune therapy'
- Baden-Wurttemberg Stiftung [BWST_ISF2018-046]
- German Cancer Aid [70112399]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [404521405, SFB 1389dUNITE]
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The development of anticancer vaccines has been hindered by a lack of suitable tumor-specific antigens, while IDH1R132H mutation generates a shared clonal neoepitope recognized by mutation-specific T-helper cells, providing new directions for certain cancer vaccines.
The development of anticancer vaccines as a pillar of cancer immunotherapy has been hampered by the scarcity of suitable tumor-specific antigens. While response to immune checkpoint inhibitors is driven by T cells recognizing mutated antigens, the vast majority of these neoantigens are patient-specific, mandating personalized approaches. In addition, neoantigens are often subclonal present in only a fraction of tumor cells resulting in immune evasion of neoantigen-negative tumor cells. Isocitrate dehydrogenase (IDH)1 mutations, most frequently encoding for the neomorphic protein IDH1R132H, are frequent driver mutations found in the majority of diffuse World Health Organization grade 2 and 3 gliomas. In addition, IDH1R132H generates a shared clonal neoepitope that is recognized by mutation-specific T-helper cells. A recent phase 1 trial (NOA-16, NCT02454634) demonstrated safety and immunogenicity of IDH1- vac, a long IDH1R132H peptide vaccine in patients with newly diagnosed astrocytoma and provided evidence of biological efficacy based on imaging parameters. In addition, vaccine-induced IDH1R132Hreactive tumor-infiltrating T cells were identified. Here we discuss clinical and scientific implications and future developments of IDH-directed immunotherapies.
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