Target intelligence / Profile preview

Isocitrate dehydrogenase 1 R132H neoepitope (IDH1R132H neoepitope)

Target
IDH1R132H neoepitope
Molecular classification
Enzyme (isocitrate dehydrogenase family, specifically a mutant form), Neoepitope (mutation-derived antigenic peptide), Other (tumor neoantigen)
01

Overview

The **IDH1R132H neoepitope** is a tumor-specific mutant peptide generated by the R132H point mutation in the isocitrate dehydrogenase 1 (IDH1) enzyme. This mutation results in a neomorphic enzyme activity that produces the oncometabolite D-2-hydroxyglutarate, leading to wide-ranging epigenetic and metabolic disturbances that drive tumorigenesis. The neoepitope generated by this mutation can be presented by MHC class II molecules, making it a promising immunotherapeutic target. Peptide vaccines targeting the IDH1R132H neoepitope are in clinical trials for glioma and have demonstrated the induction of specific T-helper immune responses and early safety. The IDH1R132H mutation is a driver in several cancers, particularly astrocytomas and other gliomas, and has also been therapeutically targeted by small molecule IDH1 inhibitors[1][2][3][5].

Other names
IDH1(R132H) neoepitopeMutant IDH1 neoepitopeIDH1-mutant neoepitope (R132H)IDH1R132H peptide
02

Mechanism of action

IDH1 inhibitors: block the neomorphic catalytic activity of mutant IDH1, reducing oncometabolite (D-2HG) production[2][3] Peptide vaccine: induces neoantigen-specific CD4+ T cell response, leading to immune attack against tumor cells presenting the IDH1R132H neoepitope on MHC class II[1][3]

03

Biological functions

Catalysis of isocitrate to α-ketoglutarate (wild type function of IDH1)Generation of D-2-hydroxyglutarate through neomorphic activity in mutant formImmune response (as neoepitope presented on MHC class II)Cellular metabolism deregulation (indirect via mutation effect)Epigenetic modification (indirect via oncometabolite D-2HG)
04

Disease associations

Cancer (most notably low-grade and high-grade gliomas, acute myeloid leukemia, and other cancers with IDH1 mutations)
05

Safety considerations

Long-term toxicities associated with IDH inhibitors (e.g., cytopenias, transaminitis)[3]Vaccine: mostly low-grade immune-mediated adverse events; potential for autoimmune reactivity, pseudoprogression, and blood-brain barrier disruption[1][3]
06

Interacting drugs

Vorasidenib (FDA-approved IDH inhibitor for IDH1-mutant gliomas)[3]

2 more in the full profile.

07

Biomarkers

IDH1R132H mutation (molecular testing of tumor)D-2-hydroxyglutarate levels (functional surrogate biomarker)Neoantigen-specific T cell responses (immunologic monitoring)[1][3]

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