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Seminars in Immunopathology
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Open Access 01-08-2024 | Cytokines | Review

Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy

Authors: Andrew D. Hughes, David T. Teachey, Caroline Diorio

Published in: Seminars in Immunopathology | Issue 3-4/2024

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Abstract

The advent of chimeric antigen receptor T cells (CAR-T) has been a paradigm shift in cancer immunotherapeutics, with remarkable outcomes reported for a growing catalog of malignancies. While CAR-T are highly effective in multiple diseases, salvaging patients who were considered incurable, they have unique toxicities which can be life-threatening. Understanding the biology and risk factors for these toxicities has led to targeted treatment approaches which can mitigate them successfully. The three toxicities of particular interest are cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS). Each of these is characterized by cytokine storm and hyperinflammation; however, they differ mechanistically with regard to the cytokines and immune cells that drive the pathophysiology. We summarize the current state of the field of CAR-T-associated toxicities, focusing on underlying biology and how this informs toxicity management and prevention. We also highlight several emerging agents showing promise in preclinical models and the clinic. Many of these established and emerging agents do not appear to impact the anti-tumor function of CAR-T, opening the door to additional and wider CAR-T applications.
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Metadata
Title
Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy
Authors
Andrew D. Hughes
David T. Teachey
Caroline Diorio
Publication date
01-08-2024
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 3-4/2024
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-024-01013-w

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