Isocitrate dehydrogenase 1 (R132H) neoantigen presented on MHC class II (IDH1-R132H-MHCII)

The Isocitrate dehydrogenase 1 (IDH1) (R132H) neoantigen presented on MHC class II is a highly specific tumor antigen found in the majority of low-grade gliomas and secondary glioblastomas. This neoantigen arises from a somatic point mutation (R132H) that creates a novel peptide sequence capable of being presented by Major Histocompatibility Complex (MHC) class II molecules, particularly the HLA-DRB1*01:01 allele (Schumacher et al., Nature 2014). Unlike wild-type IDH1, this mutant form is recognized as foreign by the immune system, making it an ideal target for precision immunotherapy such as the IDH1-vac peptide vaccine (Platten et al., Nature 2021). Recognition of this epitope by CD4+ T helper cells is crucial for orchestrating a comprehensive anti-tumor immune response, including the recruitment and activation of other immune effectors. Because the IDH1 mutation is a clonal, early-stage event in glioma development, targeting this neoantigen ensures that the majority of tumor cells are susceptible to immune attack. However, the effectiveness of targeting this neoantigen can be hindered by the immunosuppressive tumor microenvironment, often driven by the accumulation of the oncometabolite (R)-2-hydroxyglutarate (Bunse et al., Nature Medicine 2018). Clinical trials have demonstrated that vaccines targeting this specific peptide-MHC complex are safe and can induce robust, long-lasting mutation-specific T-cell responses in patients.

Other names

IDH1-R132H neoepitopeIDH1-R132H peptide-HLA-DR complexIDH1-vac targetMutant IDH1 antigenIDH1 R132H peptide presented on HLA-DRB1*01:01

Induction of mutation-specific CD4+ T-cell responses through the presentation of the IDH1 R132H peptide on MHC class II molecules, leading to anti-tumor immunity.