The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas
Open accessAbstract
Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1–5 are aggressive and universally fatal pediatric brain cancers6. Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies7–10, and recent results suggest benefit in central nervous system malignancies11–13. Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2. Anti-GD2 CAR T cells incorporating a 4-1BBz costimulatory domain14 demonstrated robust antigen-dependent cytokine generation and killing of DMG cells in vitro. In five independent patient-derived H3-K27M+ DMG orthotopic xenograft models, systemic administration of GD2-targeted CAR T cells cleared engrafted tumors except for a small number of residual GD2lo glioma cells. To date, GD2-targeted CAR T cells have been well tolerated in clinical trials15–17. Although GD2-targeted CAR T cell administration was tolerated in the majority of mice bearing orthotopic xenografts, peritumoral neuroinflammation during the acute phase of antitumor activity resulted in hydrocephalus that was lethal in a fraction of animals. Given the precarious neuroanatomical location of midline gliomas, careful monitoring and aggressive neurointensive care management will be required for human translation. With a cautious multidisciplinary clinical approach, GD2-targeted CAR T cell therapy for H3-K27M+ diffuse gliomas of pons, thalamus and spinal cord could prove transformative for these lethal childhood cancers. Lethal pediatric tumors bearing a particular histone H3 mutation upregulate the disialoganglioside GD2, thereby making these tumors susceptible to chimeric antigen receptor T cell–based immunotherapy.
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Cites
The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary
Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K., Ohgaki, H., Wiestler, O. D., Kleihues, P., & Ellison, D. W. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1545-1 · Cited by 15,657
The 2007 WHO Classification of Tumours of the Central Nervous System
Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., Scheithauer, B. W., & Kleihues, P. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0243-4 · Cited by 15,397
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
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Structural and functional features of central nervous system lymphatic vessels
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Self-citationDriver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
Schwartzentruber, J., Korshunov, A., Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tönjes, M., et al. (2012) · Nature · doi:10.1038/nature10833 · Cited by 2,631
Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia
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Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy
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Cited by
Recent advances and discoveries in the mechanisms and functions of CAR T cells
Larson, R. C., & Maus, M. V. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00323-z · Cited by 852
Brain immunology and immunotherapy in brain tumours
Sampson, J. H., Gunn, M. D., Fecci, P. E., & Ashley, D. M. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0224-7 · Cited by 722
Majzner, R. G., Theruvath, J. L., Nellan, A., Heitzeneder, S., Cui, Y., Mount, C. W., Rietberg, S. P., Linde, M. H., Xu, P., Rota, C., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0432 · Cited by 681
Self-citationClinical lessons learned from the first leg of the CAR T cell journey
Majzner, R. G., & Mackall, C. L. (2019) · Nature Medicine · doi:10.1038/s41591-019-0564-6 · Cited by 636
Self-citationEpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors
Li, D., Guo, X., Yang, K., Yang, Y., Zhou, W., Huang, Y., Liang, X., Su, J., Jiang, L., Li, J., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg9721 · Cited by 97
Metadata
- Authors
- Mount, C. W., Majzner, R. G., Sundaresh, S., Arnold, E. P., Kadapakkam, M., Haile, S., Labanieh, L., Hulleman, E., Woo, P. J., Rietberg, S. P., Vogel, H., Monje, M., & Mackall, C. L.
- Venue
- Nature Medicine
- Published
- 2018-04-16
- Volume
- 24
- Issue
- 5
- Pages
- 572-579
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2803040262
- Cited by
- 499
- References
- 50
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- green
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- Mount, C. W., Majzner, R. G., Sundaresh, S., Arnold, E. P., Kadapakkam, M., Haile, S., Labanieh, L., Hulleman, E., Woo, P. J., Rietberg, S. P., Vogel, H., Monje, M., & Mackall, C. L. (2018). Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas. Nature Medicine. https://doi.org/10.1038/s41591-018-0006-x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
