PMID- 38306431 OWN - NLM STAT- MEDLINE DCOM- 20240205 LR - 20240206 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 10 IP - 5 DP - 2024 Feb 2 TI - H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient. PG - eadi9091 LID - 10.1126/sciadv.adi9091 [doi] LID - eadi9091 AB - H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive T cell receptors and identified critical, conserved motifs in their complementarity-determining region 3 regions. Using detailed HLA mapping, we further demonstrate that diverse HLA-DQ and HLA-DR alleles present immunogenic H3K27M epitopes. Furthermore, we identified and profiled H3K27M-reactive B cell receptors from activated B cells in the cerebrospinal fluid. Our results uncover the breadth of the adaptive immune response against a shared clonal neoantigen across multiple HLA allelotypes and support the use of class II-restricted peptide vaccines to stimulate tumor-specific T and B cells harboring receptors with therapeutic potential. FAU - Boschert, Tamara AU - Boschert T AUID- ORCID: 0009-0007-8957-5319 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. AD - Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ, Mainz, Germany. FAU - Kromer, Kristina AU - Kromer K AUID- ORCID: 0009-0005-5617-7635 AD - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. AD - BioMed X GmbH, Heidelberg, Germany. FAU - Lerner, Taga AU - Lerner T AD - BioMed X GmbH, Heidelberg, Germany. FAU - Lindner, Katharina AU - Lindner K AUID- ORCID: 0000-0002-2735-3266 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. AD - Immune Monitoring Unit, DKFZ and National Center for Tumour Diseases (NCT), Heidelberg, Germany. FAU - Haltenhof, Gordon AU - Haltenhof G AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Tan, Chin Leng AU - Tan CL AUID- ORCID: 0000-0002-2529-1030 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. FAU - Jahne, Kristine AU - Jahne K AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Poschke, Isabel AU - Poschke I AUID- ORCID: 0000-0002-4387-5566 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Immune Monitoring Unit, DKFZ and National Center for Tumour Diseases (NCT), Heidelberg, Germany. FAU - Bunse, Lukas AU - Bunse L AUID- ORCID: 0000-0002-4490-7574 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. FAU - Eisele, Philipp AU - Eisele P AUID- ORCID: 0000-0001-6831-4282 AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. FAU - Grassl, Niklas AU - Grassl N AUID- ORCID: 0000-0001-7987-0444 AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. FAU - Mildenberger, Iris AU - Mildenberger I AUID- ORCID: 0009-0008-8825-4908 AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. FAU - Sahm, Katharina AU - Sahm K AUID- ORCID: 0000-0001-7694-0988 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. FAU - Platten, Michael AU - Platten M AUID- ORCID: 0000-0002-4746-887X AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ, Mainz, Germany. AD - Immune Monitoring Unit, DKFZ and National Center for Tumour Diseases (NCT), Heidelberg, Germany. AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. AD - DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim Germany. FAU - Lindner, John M AU - Lindner JM AUID- ORCID: 0000-0002-4940-5354 AD - BioMed X GmbH, Heidelberg, Germany. FAU - Green, Edward W AU - Green EW AUID- ORCID: 0000-0003-1922-2298 AD - CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. AD - Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany. LA - eng PT - Journal Article DEP - 20240202 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 0 (HLA-DR Antigens) RN - 0 (Epitopes) SB - IM CIN - doi: 10.1126/sciadv.adk3060 MH - Humans MH - *T-Lymphocytes MH - HLA-DR Antigens MH - Vaccination MH - *Glioma/genetics MH - Epitopes PMC - PMC10836722 EDAT- 2024/02/02 18:42 MHDA- 2024/02/05 06:43 PMCR- 2024/02/02 CRDT- 2024/02/02 14:05 PHST- 2024/02/05 06:43 [medline] PHST- 2024/02/02 18:42 [pubmed] PHST- 2024/02/02 14:05 [entrez] PHST- 2024/02/02 00:00 [pmc-release] AID - adi9091 [pii] AID - 10.1126/sciadv.adi9091 [doi] PST - ppublish SO - Sci Adv. 2024 Feb 2;10(5):eadi9091. doi: 10.1126/sciadv.adi9091. Epub 2024 Feb 2.