and M.S. provided the GMP facility for generating peptide emulsion. S.S. synthesized peptides. W.W. conceptualized the trial, interpreted data, and wrote the paper. Funding Open access funding provided by Deutsches Krebsforschungszentrum (DKFZ). Competing interests M.P., T.B. and W.W. are inventors and patent-holders on ‘Peptides for use in treating or diagnosing IDH1R132H positive cancers’ (EP2800580B1). Additional information Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41586-021-03363-z. Correspondence and requests for materials should be addressed to M.P.Peer review information Nature thanks Cornelis Melief, Vicky Wu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Reprints and permissions information is available at http://www.nature.com/reprints. Article Extended Data Fig. 1 | See next page for caption. Extended Data Fig. 1 | Trial design and recruitment. a, Patient disposition CONSORT flow diagram. Forty-four patients were enrolled and screened across 7 trial sites, of which 11 were excluded. Of 33 allocated patients, 32 received the intervention. Twenty-eight patients completed the study, because four discontinued the intervention owing to disease progression. The safety dataset (SDS) for analysis contained all patients who received the intervention (n = 32); 30 of these were evaluable for immunogenicity and comprised the immunogenicity dataset (IDS) ( n = 30). b, Study flow chart. The trial population comprised three treatment groups (arms) according to the standard therapy received. IDH1-vac was administered at V03 (week 1), V04 (week 3), V05 (week 5) V06 (week 7), V07 (week 11), V08 (week 15), V09 (week 19), and V10 (week 23). Blood for primary endpoint immunogenicity testing was drawn at V03 (baseline), V05, V07, V10, V12 (week 35, safety follow-up (SFU)), and V13 (week 47, EOS). MRI scans (represented by brain images) were performed at clinical screening, V07, V10, V12, and V13. XRT, radiotherapy; TMZ, temozolomide; cTMZ, concomitant TMZ, RT + TMZ; aTMZ, adjuvant TMZ. TMZ cycle numbers indicated. Article Extended Data Fig. 2 | Serum cytokine levels during treatment with IDH1-vac. Heat maps depicting longitudinal (V03–V13) cytokine concentrations in sera from transient ( n = 16) and sustained ( n = 9) T cell responder patients, measured by multiplex bead technology. For definition of transient and sustained responses, see Methods. White, sample not available; red, concentration out of depicted range. Extended Data Fig. 3 | Relationship between MHC alleles and T cell response. a, Venn diagram of T cell non-responders and B cell non-responders in the IDS. b , c, Allele prevalence of MHC class I supertype families ( b), and MHC class II DRB1* alleles with a total prevalence of three or more, and paralogues (c). Grey, numbers of alleles present or absent (for paralogues) in patients with T cell responses to IDH1-vac (T cell response); black, numbers of alleles present or absent (for paralogues) in patients without T cell responses to IDH1-vac (T cell non-response). n (total alleles) = 64 for 32 patients in the SDS. d , IDH1 and IDH1(R132H) 20-mer p123–142 affinities to six MHCII DRB1* alleles and DRB3*, DRB4*, and DRB5* MHCII paralogues were assessed in vitro. Four alleles and DRB4* paralogue are shown as examples in the graphs. CLIP , KLAT, and PADRE represent positive control peptides. GB, good binder; B, intermediate binder; WB, weak binder; NB, non-binder. n = 1 of 2 independent experiments. e, Correlation analysis of in vitro MHC class II affinities with MSS. White, no affinity-tested alleles present; blue, intermediate binder(s) present; green, weak binder(s) present; black, non-binders present. n = 30 patients in the IDS. Article Extended Data Fig. 4 | T cell immunogenicity and standard treatment in the IDS. a, b, T cell immune responses assessed by MSS (top) and by immune response criteria for positivity over time (bottom) according to concomitant use of steroids until EOT ( a) and primary SOC treatment ( b). Top, individual values and median.