Neoepitope-specific vaccination of a patient with diffuse midline glioma targeting H3K27M induces polyclonal B and T cell responses across diverse HLA alleles
Boschert, T.; Kromer, K.; Lerner, T.; Lindner, K.; Haltenhof, G.; Tan, C. L.; Jahne, K.; Poschke, I.; Bunse, L.; Grassl, N.; Mildenberger, I.; Sahm, K.; Platten, M.; Lindner, J. M.; Green, E. W.
Show abstract
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 who was treated with an H3K27M peptide vaccine and subsequently entered complete remission. The vaccine robustly expanded class II 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 CDR3 regions. Using detailed HLA mapping, we further demonstrate that diverse HLA-DQ, and -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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- LAG-3 blockade reactivates the CD8+ T cell expansion program to re-expand contracted clones in the tumor 98%
- APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence 98%
- Agonistic CD40 antibody therapy induces tertiary lymphoid structures but impairs the response to immune checkpoint blockade in glioma 97%
Similar papers in this journal
- Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumour immunity 96%
- Cell lineage as a predictor of immune response in neuroblastoma 95%
- Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.