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IMMUNOTHERAPY

Modeling cytokine release syndrome

Nature Medicine volume 24, pages 705–706 (2018)Cite this article

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Complete leukemic responses to chimeric antigen receptor–modified T cells are invariably accompanied by severe toxicity. Recently developed animal models allow mechanistic dissection and prevention of toxicity without loss of therapeutic benefit.

The adoptive transfer of T cells modified with chimeric antigen receptors (CARs) targeting the B cell antigen CD19 offers permanent cures in patients with B cell leukemia, without the devastating long-term toxicities of conventional, less-targeted therapies1. These benefits, however, require patients to endure and survive the almost invariable short-term toxicity of cytokine release syndrome (CRS) and, less commonly, neurotoxicity. CRS is an inflammatory response syndrome characterized by high fevers, myalgia and malaise, and in severe cases, vascular leak with hypotension, hypoxia, coagulopathy, multiorgan toxicity and even death2. CRS occurring after CD19.CAR T cell (CAR-T) infusion is frequently followed, within days, by neurotoxicity characterized by prolonged headaches, reduced consciousness and delirium, with more severe cases developing cerebral bleeds, seizures and death3. The severity of neurotoxicity correlates with the number of CAR-Ts infused, tumor burden and the severity of CRS4.

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Fig. 1: Modeling CRS after CAR T cell transfer in mice reveals macrophages to be key players in the development of CRS and neurotoxicity.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Cliona Rooney & Tim Sauer

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  1. Cliona Rooney
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  2. Tim Sauer
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Correspondence to Cliona Rooney.

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The authors declare no competing interests.

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Rooney, C., Sauer, T. Modeling cytokine release syndrome. Nat Med 24, 705–706 (2018). https://doi.org/10.1038/s41591-018-0068-9

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