![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB |
![[thumbnail of Supplementary Materials]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Materials)
1MB |
| Item Type: | Article |
|---|---|
| Title: | H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2(+) patients with diffuse midline glioma |
| Creators Name: | Immisch, L., Papafotiou, G., Popp, O., Mertins, P., Blankenstein, T. and Willimsky, G. |
| Abstract: | Diffuse midline glioma is the leading cause of solid cancer-related deaths in children with very limited treatment options. A majority of the tumors carry a point mutation in the histone 3 variant (H3.3) creating a potential HLA-A*02:01 binding epitope (H3.3K27M(26-35)). Here, we isolated an H3.3K27M-specific T cell receptor (TCR) from transgenic mice expressing a diverse human TCR repertoire. Despite a high functional avidity of H3.3K27M-specific T cells, we were not able to achieve recognition of cells naturally expressing the H3.3K27M mutation, even when overexpressed as a transgene. Similar results were obtained with T cells expressing the published TCR 1H5 against the same epitope. CRISPR/Cas9 editing was used to exclude interference by endogenous TCRs in donor T cells. Overall, our data provide strong evidence that the H3.3K27M mutation is not a suitable target for cancer immunotherapy, most likely due to insufficient epitope processing and/or amount to be recognized by HLA-A*02:01 restricted CD8(+) T cells. |
| Keywords: | CD8-Positive T-Lymphocytes, Epitopes, Glioma, HLA-A2 Antigen, Histones, Immunotherapy, Transgenic Mice, Mutation, Antigen, T-Cell Receptors, Animals, Mice |
| Source: | Journal for ImmunoTherapy of Cancer |
| ISSN: | 2051-1426 |
| Publisher: | BMJ Publishing Group |
| Volume: | 10 |
| Number: | 10 |
| Page Range: | e005535 |
| Date: | 27 October 2022 |
| Official Publication: | https://doi.org/10.1136/jitc-2022-005535 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
