A vaccine targeting mutant IDH1 in newly diagnosed glioma

Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1-3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5...

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Main Authors: Platten, Michael (Author) , Bunse, Lukas (Author) , Wick, Antje (Author) , Bunse, Theresa (Author) , Le Cornet, Lucian (Author) , Harting, Inga (Author) , Sahm, Felix (Author) , Sanghvi, Khwab (Author) , Tan, Chin Leng (Author) , Poschke, Isabel (Author) , Green, Edward (Author) , Justesen, Sune (Author) , Behrens, Geoffrey A. (Author) , Breckwoldt, Michael O. (Author) , Freitag, Angelika (Author) , Rother, Lisa-Marie (Author) , Schmitt, Anita (Author) , Schnell, Oliver (Author) , Hense, Jörg (Author) , Misch, Martin (Author) , Krex, Dietmar (Author) , Stevanovic, Stefan (Author) , Tabatabai, Ghazaleh (Author) , Steinbach, Joachim P. (Author) , Bendszus, Martin (Author) , Deimling, Andreas von (Author) , Schmitt, Michael (Author) , Wick, Wolfgang (Author)
Format: Article (Journal)
Language:English
Published: 24 March 2021
In: Nature
Year: 2021, Volume: 592, Pages: 463-468
ISSN:1476-4687
DOI:10.1038/s41586-021-03363-z
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41586-021-03363-z
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41586-021-03363-z
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Author Notes:Michael Platten, Lukas Bunse, Antje Wick, Theresa Bunse, Lucian Le Cornet, Inga Harting, Felix Sahm, Khwab Sanghvi, Chin Leng Tan, Isabel Poschke, Edward Green, Sune Justesen, Geoffrey A. Behrens, Michael O. Breckwoldt, Angelika Freitag, Lisa-Marie Rother, Anita Schmitt, Oliver Schnell, Jörg Hense, Martin Misch, Dietmar Krex, Stefan Stevanovic, Ghazaleh Tabatabai, Joachim P. Steinbach, Martin Bendszus, Andreas von Deimling, Michael Schmitt & Wolfgang Wick

MARC

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520 |a Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1-3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H)+ tumours in syngeneic MHC-humanized mice4,6-8. Here we describe a multicentre, single-arm, open-label, first-in-humans phase I trial that we carried out in 33 patients with newly diagnosed World Health Organization grade 3 and 4 IDH1(R132H)+ astrocytomas (Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), ClinicalTrials.gov identifier NCT02454634). 
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