Isocitrate dehydrogenase 1 (IDH1) R132H mutant peptide-MHC complex (IDH1-R132H pMHC)

The Isocitrate dehydrogenase 1 (IDH1) R132H mutant peptide-MHC complex is a tumor-specific neoantigen found in the majority of lower-grade gliomas and secondary glioblastomas. The R132H mutation is a driver event that results in a gain-of-function enzymatic activity, producing the oncometabolite 2-hydroxyglutarate, but it also creates a unique amino acid sequence that can be processed and presented by the Major Histocompatibility Complex (MHC), specifically HLA-DRB1*01:01. Because this mutant peptide is entirely absent in healthy tissues, it represents an ideal target for precision immunotherapy, including peptide-based vaccines and T-cell receptor (TCR) engineered adoptive cell therapies. Targeting this complex allows the immune system to selectively identify and destroy glioma cells while sparing normal brain cells expressing wild-type IDH1. Clinical trials, such as the NOA-16 study, have demonstrated that vaccines targeting this pMHC complex are safe and capable of inducing robust, mutation-specific T-cell responses in patients with newly diagnosed gliomas (Platten et al., Nature 2021; Schumacher et al., Nature 2014).

Other names

IDH1 R132H neoantigenIDH1 R132H peptide-HLA complexMutant IDH1 R132H epitopeIDH1-R132H neoepitope

Induction of mutation-specific CD4+ and CD8+ T-cell responses that recognize and eliminate tumor cells presenting the IDH1-R132H neoepitope on their surface MHC molecules.