Issue 37, 2022

Emerging approaches for preventing cytokine release syndrome in CAR-T cell therapy

Abstract

Chimeric antigen receptor (CAR) T cells have demonstrated remarkable anti-tumor efficacy against hematological malignancies, such as leukemia and lymphoma. However, patients treated with CAR-T cells frequently experience cytokine release syndrome (CRS), one of the most life-threatening adverse events of the therapy induced by systemic concentrations of pro-inflammatory cytokines throughout the body. Immunosuppressants such as tocilizumab are currently administered to treat the onset and progression of CRS symptoms. In order to reduce the risk of CRS, newly designed next-generation CAR-T treatments are being developed for both hematopoietic malignancies and solid tumors. In this review, we discuss six classes of interesting approaches that control cytokine production of CAR-T cell therapy: adaptor-based strategies, orthogonal cytokine–receptor pairs, regulation of macrophage cytokine activity, autonomous neutralization of key cytokines, kill switches and methods of reversible suppression of CARs. With these strategies, future CAR-T cell therapies will be designed to preemptively inhibit CRS, minimize the patients’ suffering, and maximize the number of benefiting patients.

Graphical abstract: Emerging approaches for preventing cytokine release syndrome in CAR-T cell therapy

Article information

Article type
Review Article
Submitted
20 mar 2022
Accepted
08 jul 2022
First published
18 jul 2022
This article is Open Access
Creative Commons BY license

J. Mater. Chem. B, 2022,10, 7491-7511

Emerging approaches for preventing cytokine release syndrome in CAR-T cell therapy

S. Balagopal, K. Sasaki, P. Kaur, M. Nikolaidi and J. Ishihara, J. Mater. Chem. B, 2022, 10, 7491 DOI: 10.1039/D2TB00592A

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