CART Cell Toxicities: New Insight into Mechanisms and Management

Authors

Anas Zahid^1, , Elizabeth L. Siegler^{2, 3}, Saad S. Kenderian^{2, 3, 4, 5, *,}

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

DOI

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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TY  - JOUR
AU  - Anas Zahid
AU  - Elizabeth L. Siegler
AU  - Saad S. Kenderian
PY  - 2020
DA  - 2020/11/23
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  - 10.2991/chi.k.201108.001
ID  - Zahid2020
ER  -