H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient

• DOI: 10.1126/sciadv.adi9091
• Publication Date: 2024-02-02T18:58:50Z
• Authors: Tamara Boschert; Kristina Kromer; Taga Lerner; Katharina Lindner; Gordon Haltenhof; Chin Leng Tan; Kristine Jähne; Isabel Poschke; Lukas Bunse; Philipp Eisele; Niklas Grassl; Iris Mildenberger; Katharina Sahm; Michael Platten; John M. Lindner; Edward W. Green
• Keywords: Epitopes; 0303 health sciences; 03 medical and health sciences; T-Lymphocytes; Vaccination; Humans; Biomedicine and Life Sciences; HLA-DR Antigens; Glioma

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma poor survival. We functionally dissect the immune response one patient treated H3K27M peptide vaccine who subsequently entered complete remission. The robustly expanded class II human leukocyte antigen (HLA)–restricted peripheral H3K27M-specific cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive receptors identified critical, conserved motifs in their complementarity-determining region 3 regions. detailed HLA mapping, further demonstrate that diverse HLA-DQ HLA-DR alleles present immunogenic epitopes. Furthermore, profiled from activated cells cerebrospinal fluid. Our results uncover breadth adaptive against shared clonal neoantigen across multiple allelotypes support use II–restricted vaccines to stimulate tumor-specific harboring therapeutic potential.