The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety
Open accessAbstract
Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3–specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation. Significance: This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF. This article is highlighted in the In This Issue feature, p. 1
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Metadata
- Authors
- Vitanza, N. A., Wilson, A. L., Huang, W., Seidel, K., Brown, C., Gustafson, J. A., Yokoyama, J. K., Johnson, A. J., Baxter, B. A., Koning, R. W., Reid, A. N., Meechan, M., Biery, M. C., Myers, C., Rawlings-Rhea, S. D., Albert, C. M., Browd, S. R., Hauptman, J. S., Lee, A., Ojemann, J. G., Berens, M. E., Dun, M. D., Foster, J. B., Crotty, E. E., Leary, S. E. S., Cole, B. L., Perez, F. A., Wright, J. N., Orentas, R. J., Chour, T., Newell, E. W., Whiteaker, J. R., Zhao, L., Paulovich, A. G., Pinto, N., Gust, J., Gardner, R. A., Jensen, M. C., & Park, J. R.
- Venue
- Cancer Discovery
- Published
- 2022-10-19
- Volume
- 13
- Issue
- 1
- Pages
- 114-131
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W4306795470
- Cited by
- 279
- References
- 64
- FWCI
- 19.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety. https://app.cochat.ai/papers/10.1158/2159-8290.cd-22-0750
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- Vitanza, N. A., Wilson, A. L., Huang, W., Seidel, K., Brown, C., Gustafson, J. A., Yokoyama, J. K., Johnson, A. J., Baxter, B. A., Koning, R. W., Reid, A. N., Meechan, M., Biery, M. C., Myers, C., Rawlings-Rhea, S. D., Albert, C. M., Browd, S. R., Hauptman, J. S., Lee, A., . . . Park, J. R. (2023). Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-22-0750
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
