The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
Open accessPublished version of a preprint
Abstract
Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy. Experimental Design: Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intraventricular TCR-transgenic T-cell therapy was assessed in a newly developed glioma model in MHC-humanized mice induced by CRISPR-based delivery of tumor suppressor–targeting guide RNAs. Results: We identify recurrent capicua transcriptional repressor (CIC) inactivating hotspot mutations at position 215 CICR215W/Q as immunogenic MHC class II (MHCII)-restricted neoepitopes. Vaccination of MHC-humanized mice resulted in the generation of robust MHCII-restricted mutation-specific T-cell responses against CICR215W/Q. Adoptive intraventricular transfer of CICR215W-specific TCR-transgenic T cells exert antitumor responses against CICR215W-expressing syngeneic gliomas. Conclusions: The integration of immunocompetent MHC-humanized orthotopic glioma models in the discovery of shared immunogenic glioma neoepitopes facilitates the identification and preclinical testing of human leukocyte antigen (HLA)-restricted neoepitope-specific TCRs for locoregional TCR-transgenic T-cell adoptive therapy.
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“Recently, a murine model system was developed that circumvents this limitation by using an HLA-A*02:01-transgenic murine GBM tumour cell line, which can be transfected with human TAAs and implanted intracranially into immunocompetent HLA-A*02:01-transgenic mice [46].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [46]
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circlize implements and enhances circular visualization in R
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Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy
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Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial
Keskin, D. B., Anandappa, A. J., Sun, J., Tirosh, I., Mathewson, N. D., Li, S., Oliveira, G., Giobbie-Hurder, A., Felt, K., Gjini, E., et al. (2019) · Nature · doi:10.1038/s41586-018-0792-9 · Cited by 1,432
Mutant MHC class II epitopes drive therapeutic immune responses to cancer
Kreiter, S., Vormehr, M., van de Roemer, N., Diken, M., Löwer, M., Diekmann, J., Boegel, S., Schrörs, B., Vascotto, F., Castle, J. C., et al. (2015) · Nature · doi:10.1038/nature14426 · Cited by 1,243
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Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma
Lutz, J., Feist, R. K., Sonntag, T., Peguero-Sánchez, E., Wolter, K., Bick, R., Bauer, J., Walz, J. S., & Heidenreich, R. (2025) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-025-04178-x · Cited by 9
“Recently, a murine model system was developed that circumvents this limitation by using an HLA-A*02:01-transgenic murine GBM tumour cell line, which can be transfected with human TAAs and implanted intracranially into immunocompetent HLA-A*02:01-transgenic mice [46].”
Metadata
- Authors
- Kilian, M., Friedrich, M., Sanghvi, K., Green, E., Pusch, S., Kawauchi, D., Löwer, M., Sonner, J. K., Krämer, C., Zaman, J., Jung, S., Breckwoldt, M. O., Willimsky, G., Eichmüller, S. B., von Deimling, A., Wick, W., Sahm, F., Platten, M., & Bunse, L.
- Affiliations
- German Cancer Research Center (DE)
- Johannes Gutenberg University Mainz (DE)
- 4DKTK Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Corresponding author
- Bunse, Lukas
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2021-11-15
- Volume
- 28
- Issue
- 2
- Pages
- 378-389
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC9401455
- OpenAlex
- W3213468635
- Cited by
- 18
- References
- 55
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 1
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- German Research Foundation (404521405)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- glioma, MHC class II restriction, T cell receptor transgenic T cells, adoptive T cell therapy, tumor suppressor mutations, adoptive immunotherapy
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Disease Models, Animal, Glioma, Immunotherapy, Neoplasm Recurrence, Local, T-Lymphocytes, Immunotherapy, Adoptive, Mice
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