Work

P03.06 Deciphering vaccine-induced neoepitope-specific T cell responses in a patient with H3K27M-mutant midline glioma WHO grade 4

Year: 2021

Type: conference-abstract

Abstract: Background K27M-mutant histone-3 (H3K27M) defines a clinically and molecularly distinct entity of diffuse midline gliomas WHO grade 4 with an unfavorable prognosis. From an immunological perspective, H3K27M constitutes a cancer neoepitope: in a syngeneic MHC-humanized mouse model, an H3K27M-specific long peptide vaccine induced mutation-specific T cells responses capable of inhibiting growth of H3K27M-expressing tumors. Materials and Methods Here, we describe clinical response of a patient diagnosed with H3K27M-mutant midline gliomas to H3K27M-specific peptide vaccination and exploit vaccine-induced T cell phenotypes. Results Repeated peptide vaccinations were well tolerated and resulted in long-term response after pseudoprogression. Longitudinal immune monitoring showed induction of H3K27M-specific CD4-driven T cell responses in the peripheral blood. Within the cerebrospinal fluid, expansion of HLA-specific vaccine-induced T cell receptor (TCR) clones was observed and associated with distinct HLA types. Conclusions Identification of vaccine-induced TCR clones within the peripheral blood and CSF of patients with H3K27M-mutant midline glioma may be used to prioritize TCRs for adoptive T cell therapy. Disclosure Information K. Lindner: None. K. Kromer: None. K. Jähne: None. L. Bunse: E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Patent: US20180155403A1 (Histone Anti-Cancer Vaccines). C. Tan: None. I. Poschke: None. E. Green: None. J.M. Lindner: None. M. Platten: C. Other Research Support (supplies, equipment, receipt of drugs or other in-kind support); Modest; Roche. E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Patent: US20180155403A1 (Histone Anti-Cancer Vaccines). K. Sahm: E. Ownership Interest (stock, stock options, patent or other intellectual property); Modest; Patent: US20180155403A1 (Histone Anti-Cancer Vaccines).

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2021-itoc8.28