Isocitrate dehydrogenase 1 R132H mutant peptide (IDH1 R132H (for the mutant protein), but no canonical abbreviation for the peptide form specifically)

The IDH1 R132H mutant peptide refers to a short peptide containing the amino acid substitution at position 132 in isocitrate dehydrogenase 1 (IDH1), where arginine (R) is replaced by histidine (H). This mutation is highly recurrent and specific to several cancer types, most notably low-grade gliomas and secondary glioblastomas. The mutated enzyme acquires a neomorphic activity, converting α-ketoglutarate to D-2-hydroxyglutarate (D-2HG), a metabolite that disrupts cell differentiation and promotes tumorigenesis via widespread epigenetic changes. The mutant peptide is used as a neoantigen in therapeutic vaccine strategies, aiming to trigger an immune response against tumor cells harboring this mutation. Multiple small molecules, such as ivosidenib, selectively inhibit the mutant enzyme to block oncometabolite production. The presence of the IDH1 R132H mutation is a biomarker for selecting targeted therapy and assessing prognosis. Early vaccine trials (e.g., NOA-16) demonstrate the mutation’s utility as a highly specific immunotherapeutic target, with good initial safety and immunogenicity in glioma patients.

Other names

IDH1 R132H mutantMutant IDH1 R132H peptideIDH1 R132H neoantigenMutant isocitrate dehydrogenase 1 peptide

Small molecule inhibitors: Allosteric inhibition of mutant IDH1 enzymatic activity—block the production of D-2-hydroxyglutarate Peptide vaccine: Induction of an anti-tumor CD4+ and CD8+ T-cell response specifically against IDH1 R132H-expressing tumor cells