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      Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy

      review-article

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A paradigm shift has recently occurred in the field of cancer therapeutics. Traditional anticancer agents, such as chemotherapy, radiotherapy and small-molecule drugs targeting specific signalling pathways, have been joined by cellular immunotherapies based on T cell engineering. The rapid adoption of novel, patient-specific cellular therapies builds on scientific developments in tumour immunology, genetic engineering and cell manufacturing, best illustrated by the curative potential of chimeric antigen receptor (CAR) T cell therapy targeting CD19-expressing malignancies. However, the clinical benefit observed in many patients may come at a cost. In up to one-third of patients, significant toxicities occur that are directly associated with the induction of powerful immune effector responses. The most frequently observed immune-mediated toxicities are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. This Review discusses our current understanding of their pathophysiology and clinical features, as well as the development of novel therapeutics for their prevention and/or management.

          Abstract

          This Review discusses our current understanding of the pathophysiological mechanisms of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome associated with chimeric antigen receptor (CAR) T cell therapies, and how this might be used for the prevention or management of these toxicities.

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          Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

          Journal of Clinical Investigation
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            Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

            Dear Editor, The rapid emergence of COVID-19 in Wuhan city, Hubei Province, China, has resulted in thousands of deaths [1]. Many infected patients, however, presented mild flu-like symptoms and quickly recover [2]. To effectively prioritize resources for patients with the highest risk, we identified clinical predictors of mild and severe patient outcomes. Using the database of Jin Yin-tan Hospital and Tongji Hospital, we conducted a retrospective multicenter study of 68 death cases (68/150, 45%) and 82 discharged cases (82/150, 55%) with laboratory-confirmed infection of SARS-CoV-2. Patients met the discharge criteria if they had no fever for at least 3 days, significantly improved respiratory function, and had negative SARS-CoV-2 laboratory test results twice in succession. Case data included demographics, clinical characteristics, laboratory results, treatment options and outcomes. For statistical analysis, we represented continuous measurements as means (SDs) or as medians (IQRs) which compared with Student’s t test or the Mann–Whitney–Wilcoxon test. Categorical variables were expressed as numbers (%) and compared by the χ 2 test or Fisher’s exact test. The distribution of the enrolled patients’ age is shown in Fig. 1a. There was a significant difference in age between the death group and the discharge group (p < 0.001) but no difference in the sex ratio (p = 0.43). A total of 63% (43/68) of patients in the death group and 41% (34/82) in the discharge group had underlying diseases (p = 0.0069). It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2 (p < 0.001). A total of 16% (11/68) of the patients in the death group had secondary infections, and 1% (1/82) of the patients in the discharge group had secondary infections (p = 0.0018). Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups (Fig. 1b and Supplementary Table 1). Fig. 1 a Age distribution of patients with confirmed COVID-19; b key laboratory parameters for the outcomes of patients with confirmed COVID-19; c interval from onset of symptom to death of patients with confirmed COVID-19; d summary of the cause of death of 68 died patients with confirmed COVID-19 The survival times of the enrolled patients in the death group were analyzed. The distribution of survival time from disease onset to death showed two peaks, with the first one at approximately 14 days (22 cases) and the second one at approximately 22 days (17 cases) (Fig. 1c). An analysis of the cause of death was performed. Among the 68 fatal cases, 36 patients (53%) died of respiratory failure, five patients (7%) with myocardial damage died of circulatory failure, 22 patients (33%) died of both, and five remaining died of an unknown cause (Fig. 1d). Based on the analysis of the clinical data, we confirmed that some patients died of fulminant myocarditis. In this study, we first reported that the infection of SARS-CoV-2 may cause fulminant myocarditis. Given that fulminant myocarditis is characterized by a rapid progress and a severe state of illness [3], our results should alert physicians to pay attention not only to the symptoms of respiratory dysfunction but also the symptoms of cardiac injury. Further, large-scale studies and the studies on autopsy are needed to confirm our analysis. In conclusion, predictors of a fatal outcome in COVID-19 cases included age, the presence of underlying diseases, the presence of secondary infection and elevated inflammatory indicators in the blood. The results obtained from this study also suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome” or fulminant myocarditis. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 38 kb)
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              Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

              Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.
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                Author and article information

                Contributors
                e.morris@ucl.ac.uk
                Journal
                Nat Rev Immunol
                Nat Rev Immunol
                Nature Reviews. Immunology
                Nature Publishing Group UK (London )
                1474-1733
                1474-1741
                17 May 2021
                : 1-12
                Affiliations
                [1 ]GRID grid.83440.3b, ISNI 0000000121901201, Department of Immunology, Institute of Immunity and Transplantation, , University College London, ; London, UK
                [2 ]GRID grid.240145.6, ISNI 0000 0001 2291 4776, Department of Lymphoma and Myeloma, , The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [3 ]GRID grid.51462.34, ISNI 0000 0001 2171 9952, Center for Cell Engineering, Sloan Kettering Institute, , Memorial Sloan Kettering Cancer Center, ; New York, NY USA
                Author information
                http://orcid.org/0000-0003-4834-1130
                http://orcid.org/0000-0003-1045-4914
                http://orcid.org/0000-0002-8716-781X
                Article
                547
                10.1038/s41577-021-00547-6
                8127450
                34002066
                ebee5676-3723-4a6f-9592-cfd0e5c18cfc
                © Springer Nature Limited 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 1 April 2021
                Categories
                Review Article

                tumour immunology,cytokines,immunotherapy
                tumour immunology, cytokines, immunotherapy

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