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Emerging targets for anticancer vaccination: IDH

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-speci...

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Bibliographic Details
Main Authors: Platten, Michael (Author) , Bunse, Lukas (Author) , Wick, Wolfgang (Author)
Format: Article (Journal)
Language:English
Published: 13 July 2021
In: ESMO open
Year: 2021, Volume: 6, Issue: 4, Pages: 1-5
ISSN:2059-7029
DOI:10.1016/j.esmoop.2021.100214
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.esmoop.2021.100214
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2059702921001757
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Author Notes:M. Platten, L. Bunse & W. Wick

MARC

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520 |a 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 IDH1R132H-reactive tumor-infiltrating T cells were identified. Here we discuss clinical and scientific implications and future developments of IDH-directed immunotherapies. 
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