Emerging targets for anticancer vaccination: IDH

ESMO Open

article

M. Platten¹  L. Bunse¹  W. Wick³ 

[1] DKTK ,(German Cancer Consortium) Clinical Cooperation Unit ,(CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center;Department of Neurology, Medical Faculty Mannheim, MCTN, University of Heidelberg;Neurology Clinic, Heidelberg University Hospital and NCT, University of Heidelberg;DKTK CCU Neurooncology

关键词: glioma;    isocitrate dehydrogenase;    neoantigen;    vaccine;    immunotherapy;   

DOI  :  10.1016/j.esmoop.2021.100214

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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.

【 授权许可】

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