The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
A vaccine targeting mutant IDH1 in newly diagnosed glioma
Open accessAbstract
Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma 1–3. 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 II 4,5. 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 mice 4,6–8. 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). The trial met its primary safety endpoint, with vaccine-related adverse events restricted to grade 1. Vaccine-induced immune responses were observed in 93.3% of patients across multiple MHC alleles. Three-year progression-free and death-free rates were 0.63 and 0.84, respectively. Patients with immune responses showed a two-year progression-free rate of 0.82. Two patients without an immune response showed tumour progression within two years of first diagnosis. A mutation-specificity score that incorporates the duration and level of vaccine-induced IDH1(R132H)-specific T cell responses was associated with intratumoral presentation of the IDH1(R132H) neoantigen in pre-treatment tumour tissue. There was a high frequency of pseudoprogression, which indicates intratumoral inflammatory reactions. Pseudoprogression was associated with increased vaccine-induced peripheral T cell responses. Combined single-cell RNA and T cell receptor sequencing showed that tumour-infiltrating CD40LG+ and CXCL13+ T helper cell clusters in a patient with pseudoprogression were dominated by a single IDH1(R132H)-reactive T cell receptor.
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Metadata
- Authors
- Platten, M., Bunse, L., Wick, A., Bunse, T., Le Cornet, L., Harting, I., Sahm, F., Sanghvi, K., Tan, C. L., Poschke, I., Green, E., Justesen, S., Behrens, G. A., Breckwoldt, M. O., Freitag, A., Rother, L.-M., Schmitt, A., Schnell, O., Hense, J., Misch, M., Krex, D., Stevanovic, S., Tabatabai, G., Steinbach, J. P., Bendszus, M., von Deimling, A., Schmitt, M., & Wick, W.
- Venue
- Nature
- Published
- 2021-03-24
- Volume
- 592
- Issue
- 7854
- Pages
- 463-468
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3137406939
- Cited by
- 432
- References
- 28
- FWCI
- 33.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Platten, M., Bunse, L., Wick, A., Bunse, T., Le Cornet, L., Harting, I., Sahm, F., Sanghvi, K., Tan, C. L., Poschke, I., Green, E., Justesen, S., Behrens, G. A., Breckwoldt, M. O., Freitag, A., Rother, L.-M., Schmitt, A., Schnell, O., Hense, J., . . . Wick, W. (2021). A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature. https://doi.org/10.1038/s41586-021-03363-z
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