Clinical Hematology International

Volume 2, Issue 4, December 2020, Pages 149 - 155

CART Cell Toxicities: New Insight into Mechanisms and Management

Authors
Anas Zahid1, ORCID, Elizabeth L. Siegler2, 3, Saad S. Kenderian2, 3, 4, 5, *, ORCID
1College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, U.A.E
2T Cell Engineering, Mayo Clinic, Rochester, MN, USA
3Division of Hematology, Mayo Clinic, Rochester, MN, USA
4Department of Immunology, Mayo Clinic, Rochester, MN, USA
5Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA
*Corresponding author. Email: Kenderian.saad@mayo.edu
Corresponding Author
Saad S. Kenderian
Received 4 September 2020, Accepted 22 October 2020, Available Online 23 November 2020.
DOI
https://doi.org/10.2991/chi.k.201108.001How to use a DOI?
Keywords
CART cell therapy, Immunotherapy, Cytokine release syndrome (CRS), Neurotoxicity
Abstract

T cells genetically engineered with chimeric antigen receptors (CART) have become a potent class of cancer immunotherapeutics. Numerous clinical trials of CART cells have revealed remarkable remission rates in patients with relapsed or refractory hematologic malignancies. Despite recent clinical success, CART cell therapy has also led to significant morbidity and occasional mortality from associated toxicities. Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) present barriers to the extensive use of CART cell therapy in the clinic. CRS can lead to fever, hypoxia, hypotension, coagulopathies, and multiorgan failure, and ICANS can result in cognitive dysfunction, seizures, and cerebral edema. The mechanisms of CRS and ICANS are becoming clearer, but many aspects remain unknown. Disease type and burden, peak serum CART cell levels, CART cell dose, CAR structure, elevated pro-inflammatory cytokines, and activated myeloid and endothelial cells all contribute to CART cell toxicity. Current guidelines for the management of toxicities associated with CART cell therapy vary between clinics, but are typically comprised of supportive care and treatment with corticosteroids or tocilizumab, depending on the severity of the symptoms. Acquiring a deeper understanding of CART cell toxicities and developing new management and prevention strategies are ongoing. In this review, we present findings in the mechanisms and management of CART cell toxicities.

Copyright
© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.
Open Access
This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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Journal
Clinical Hematology International
Volume-Issue
2 - 4
Pages
149 - 155
Publication Date
2020/11
ISSN (Online)
2590-0048
DOI
https://doi.org/10.2991/chi.k.201108.001How to use a DOI?
Copyright
© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.
Open Access
This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Cite this article

TY  - JOUR
AU  - Anas Zahid
AU  - Elizabeth L. Siegler
AU  - Saad S. Kenderian
PY  - 2020
DA  - 2020/11
TI  - CART Cell Toxicities: New Insight into Mechanisms and Management
JO  - Clinical Hematology International
SP  - 149
EP  - 155
VL  - 2
IS  - 4
SN  - 2590-0048
UR  - https://doi.org/10.2991/chi.k.201108.001
DO  - https://doi.org/10.2991/chi.k.201108.001
ID  - Zahid2020
ER  -