Emerging targets for anticancer vaccination

• Verfasst von: Platten, Michael [VerfasserIn]
• Verfasst von: Bunse, Lukas [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Titel: Emerging targets for anticancer vaccination
• Titelzusatz: IDH
• Verf.angabe: M. Platten, L. Bunse & W. Wick
• E-Jahr: 2021
• Jahr: 13 July 2021
• Umfang: 5 S.
• Fussnoten: Gesehen am 22.11.2021
• Titel Quelle: Enthalten in: ESMO open
• Ort Quelle: [London] : Elsevier, 2016
• Jahr Quelle: 2021
• Band/Heft Quelle: 6(2021), 4, Artikel-ID 100214, Seite 1-5
• ISSN Quelle: 2059-7029
• DOI: doi:10.1016/j.esmoop.2021.100214
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: glioma
• Sach-SW: immunotherapy
• Sach-SW: isocitrate dehydrogenase
• Sach-SW: neoantigen
• Sach-SW: vaccine
• K10plus-PPN: 1778222412

Abstract

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.