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Cited by 256

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Chimeric Antigen Receptor T Cell–Mediated Neurotoxicity in Nonhuman Primates

Open access
Taraseviciute, Agne, Tkachev, Victor, Ponce, Rafael, Turtle, Cameron J., Snyder, Jessica M., Liggitt, H. Denny, Myerson, David, Gonzalez-Cuyar, Luis, Baldessari, Audrey, English, Chris, Yu, Alison, Zheng, Hengqi, Furlan, Scott N., Hunt, Daniel J., Hoglund, Virginia, Finney, Olivia, Brakke, Hannah, Blazar, Bruce R., Berger, Carolina, Riddell, Stanley R., Gardner, Rebecca, Kean, Leslie S., Jensen, Michael C.·2018·Cancer Discovery
DOI 10.1158/2159-8290.cd-17-1368
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Abstract

Chimeric antigen receptor (CAR) T-cell immunotherapy has revolutionized the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (CRS) and neurotoxicity. A major barrier to developing therapeutics to prevent CAR T cell–mediated neurotoxicity is the lack of clinically relevant models. Accordingly, we developed a rhesus macaque (RM) model of neurotoxicity via adoptive transfer of autologous CD20-specific CAR T cells. Following cyclophosphamide lymphodepletion, CD20 CAR T cells expand to 272 to 4,450 cells/μL after 7 to 8 days and elicit CRS and neurotoxicity. Toxicities are associated with elevated serum IL6, IL8, IL1RA, MIG, and I-TAC levels, and disproportionately high cerebrospinal fluid (CSF) IL6, IL2, GM-CSF, and VEGF levels. During neurotoxicity, both CD20 CAR and non-CAR T cells accumulate in the CSF and in the brain parenchyma. This RM model demonstrates that CAR T cell–mediated neurotoxicity is associated with proinflammatory CSF cytokines and a pan–T cell encephalitis. Significance: We provide the first immunologically relevant, nonhuman primate model of B cell–directed CAR T-cell therapy–mediated CRS and neurotoxicity. We demonstrate CAR and non-CAR T-cell infiltration in the CSF and in the brain during neurotoxicity resulting in pan-encephalitis, accompanied by increased levels of proinflammatory cytokines in the CSF. Cancer Discov; 8(6); 750–63. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663

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Metadata

Authors
Taraseviciute, A., Tkachev, V., Ponce, R., Turtle, C. J., Snyder, J. M., Liggitt, H. D., Myerson, D., Gonzalez-Cuyar, L., Baldessari, A., English, C., Yu, A., Zheng, H., Furlan, S. N., Hunt, D. J., Hoglund, V., Finney, O., Brakke, H., Blazar, B. R., Berger, C., Riddell, S. R., Gardner, R., Kean, L. S., & Jensen, M. C.
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2018-05-31
Volume
8
Issue
6
Pages
750-763
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-17-1368
OpenAlex
W2791660181
Cited by
256
References
38
FWCI
10.95
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Chimeric Antigen Receptor T Cell–Mediated Neurotoxicity in Nonhuman Primates. https://app.cochat.ai/papers/10.1158/2159-8290.cd-17-1368
The paper
Taraseviciute, A., Tkachev, V., Ponce, R., Turtle, C. J., Snyder, J. M., Liggitt, H. D., Myerson, D., Gonzalez-Cuyar, L., Baldessari, A., English, C., Yu, A., Zheng, H., Furlan, S. N., Hunt, D. J., Hoglund, V., Finney, O., Brakke, H., Blazar, B. R., Berger, C., . . . Jensen, M. C. (2018). Chimeric Antigen Receptor T Cell–Mediated Neurotoxicity in Nonhuman Primates. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-17-1368

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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.