A H3K27M-targeted vaccine in adults with diffuse midline glioma.
- Resource Type
- Academic Journal
- Authors
- Grassl N; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.; Poschke I; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Immune Monitoring Unit, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Lindner K; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Immune Monitoring Unit, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Bunse L; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.; Mildenberger I; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.; Boschert T; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Immune Monitoring Unit, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Helmholtz Institute for Translational Oncology (HI-TRON) Mainz, German Cancer Research Center, Mainz, Germany.; Jähne K; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.; Green EW; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.; Hülsmeyer I; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Immune Monitoring Unit, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Jünger S; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Immune Monitoring Unit, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Kessler T; Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.; Suwala AK; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.; DKTK Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Eisele P; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany.; Breckwoldt MO; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.; Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.; Vajkoczy P; Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Grauer OM; Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.; Herrlinger U; Division of Clinical Neurooncology, Department of Neurology, University Hospital Bonn, University of Bonn, Bonn, Germany.; Tonn JC; Department of Neurosurgery, University of Munich LMU, Munich, Germany.; Denk M; Institute of Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Sahm F; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.; DKTK Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Bendszus M; Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany.; von Deimling A; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.; DKTK Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Winkler F; Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.; Wick W; Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.; Platten M; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.platten@dkfz-heidelberg.de.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany. m.platten@dkfz-heidelberg.de.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany. m.platten@dkfz-heidelberg.de.; Immune Monitoring Unit, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. m.platten@dkfz-heidelberg.de.; Helmholtz Institute for Translational Oncology (HI-TRON) Mainz, German Cancer Research Center, Mainz, Germany. m.platten@dkfz-heidelberg.de.; Sahm K; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. k.sahm@dkfz-heidelberg.de.; Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Mannheim, Germany. k.sahm@dkfz-heidelberg.de.; DKFZ-Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany. k.sahm@dkfz-heidelberg.de.
- Source
- Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
- Subject
- Language
- English
Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M + tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M + diffuse midline glioma on a compassionate use basis. Five patients received H3K27M-vac combined with anti-PD-1 treatment based on physician's discretion. Repeat vaccinations with H3K27M-vac were safe and induced CD4 + T cell-dominated, mutation-specific immune responses in five of eight patients across multiple human leukocyte antigen types. Median progression-free survival after vaccination was 6.2 months and median overall survival was 12.8 months. One patient with a strong mutation-specific T cell response after H3K27M-vac showed pseudoprogression followed by sustained complete remission for >31 months. Our data demonstrate safety and immunogenicity of H3K27M-vac in patients with progressive H3K27M + diffuse midline glioma.
(© 2023. The Author(s).)