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

The Isocitrate dehydrogenase 1 (IDH1) R132H neoepitope presented on MHC class II is a tumor-specific antigen found in the majority of low-grade gliomas and secondary glioblastomas (Schumacher et al., 2014). This neoepitope arises from a point mutation (arginine to histidine at position 132) that creates a unique peptide sequence not found in healthy tissue, making it an ideal target for precision immunotherapy (Platten et al., 2021). When processed and presented by Major Histocompatibility Complex (MHC) class II molecules, particularly HLA-DRB1 alleles, this complex is recognized by CD4+ T-helper cells which coordinate an anti-tumor immune response (Bunse et al., 2018). Therapeutic strategies, such as the IDH1-VAC peptide vaccine, aim to stimulate these mutation-specific T cells to eliminate tumor cells while sparing normal brain tissue (Platten et al., 2021). Because the IDH1 R132H mutation is an early, clonal event in gliomagenesis, the neoepitope is expressed throughout the tumor mass, reducing the risk of heterogeneous escape (Schumacher et al., 2014). Clinical trials have shown that targeting this neoepitope is safe and can successfully induce immune cell infiltration into the central nervous system (Platten et al., 2021).

Other names

IDH1 R132H neoantigenIDH1 R132H peptide-HLA complexMutant IDH1 neoepitopeIDH1-R132H-HLA-DRB1 complex

Induction of mutation-specific CD4+ T-helper cell responses through active immunization with a synthetic peptide encompassing the IDH1 R132H mutation, leading to anti-tumor immunity (Platten et al., 2021).