Identifying and Cloning Neoepitope Specific, CD4+ T Cells from Newly Diagnosed Glioma Patients in a Phase I Vaccination Trial Targeting Mutant IDH1

Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse gliomas, and in previous work we showed that vaccinating mice with an IDH1.R132H-specific peptide induced tumor-specific therapeutic T helper cell responses and subsequent tumors control. In a multicenter, single-arm, open-label, first-in-man phase I trial involving vaccinating 33 patients with grade 3 and 4 IDH1.R132H+ve astrocytomas we were able to show vaccine-induced immune responses in 93.3 % of patients. By combining scRNA- and T cell receptor (TCR)-sequencing, we were able to identify and clone TCRs from patients, and have gone on to show that these are IDH1.R132H reactive. These results provide new hope for patients with IDH1.R132H mutated brain tumours, and point towards future applications of such TCRs in (personalised) adoptive cell therapies.