IDH-R132H mutation is a new target for immunotherapy of low-grade glioma

Compared to high-grade glioblastomas, low-grade gliomas have relatively few immunosuppressive components and may be easier to find targets for relevant immunotherapy. IDH mutations are a common type of gene mutation in low-grade gliomas and may be a possible site for finding immunotherapy. Among them, IDH-R132H mutations tend to occur in low-grade gliomas. Serena Pellegatta et al. from the Institute of Molecular Neuro-Oncology of the Neuro-Oncology Foundation in Milan, Italy, performed immune-targeted interventions for IDH-R132H mutations in a mouse glioma model, and the results were published in Acta Neuropathol Commun in January 2015. The authors transfected the R132H mutation gene into a mouse glioma GL261 cell line to construct mIDH1-GL261 cells. In vitro experiments showed that GL261 and mIDH1-GL261 cell lines had different cell morphology but similar proliferation rates. In a mouse glioma model, magnetic resonance assay revealed that mIDH1-GL261 cell line tumors grew slower than GL261, but overall survival was similar in tumor-bearing mice. MRS and LC-MS/MS confirmed that mIDH1-GL261 cell line tumors expressed R132H and 2-HG. The authors made a peptide vaccine associated with the IDH mutation to study the effect on IDH- R132H-mutated tumors and investigated the effect of targeted immunotherapy. The survival of tumor-bearing mice was found to be prolonged after immunotherapy with the mutant IDH peptide vaccine compared to tumor-bearing mice in the control group. CD8-positive T cells, high IFN-γ expression and IDH mutant antibodies were detected within the tumor tissues receiving immunotherapy. Immunotherapy resulted in intratumoral upregulation of IFN-γ, granzyme-b and perforin-1, and downregulation of TGF-β2 and IL-10. The study conclusively determined that 25% of mIDH1-GL261 cell line tumor-bearing mice treated with immunotherapy targeting the IDH-R132H mutant locus were able to effectively induce the immune system to attack tumor cells, thereby resulted in improved survival and cure rates in the tumor-bearing mice. Therefore, the authors concluded that immune-targeted therapy for low-grade gliomas with IDH mutations has potential clinical application.