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

Balagopal, Srinivas; Sasaki, Koichi; Kaur, Pooja; Kotopoulea-Nikolaidi, Maria; Ishihara, Jun

doi:10.1039/d2tb00592a

Cited by 8 publications

(2 citation statements)

References 129 publications

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“…How to reduce or avoid the side effects of this therapy is a hot topic in research all over the world. Researchers have confirmed that the construction of CAR structure, the introduction of suicide genes into CAR-T cells, the regulation of cytokine activity in macrophages, and the autonomous neutralization of key cytokines can alleviate the symptoms of CRS ( 46 ). At the same time, combined therapy of CAR-T with programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), Ibrutinib, PI3K inhibitors and other drugs can enhance the function of CAR-T cells and reduced cytotoxicity ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy

Dou,

Ren,

Qiu

et al. 2024

Front. Med.

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BackgroundChimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.PurposeThis study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.Data sources and methodsWe searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.ResultsA total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% P = 0.338 z = −2.369 (p = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: −617.21, 95% confidence interval (−1104.41, −130.01) I[2] = 0% P = 0.88 Z = 2.48 (P = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: −11.58, 95% confidence interval (−15.28, −7.88) I[2] = 0.0% P = 0.73 z = 6.14 (p < 0.00001)].ConclusionThe prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.

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Section: Discussionmentioning

confidence: 99%

Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy

Dou,

Ren,

Qiu

et al. 2024

Front. Med.

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“…To reduce the risk of CRS, newly designed next-generation CAR-T cells therapy is being developed for hematopoietic malignancies and solid tumors. S. Balagopal et al ( 113 ) have discussed Six interesting approaches to control cytokine production in CAR-T cells 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 cells therapies will be designed to preemptively inhibit CRS, minimizing patient suffering and maximizing the number of patients who benefit.…”

Section: Strategies To Deal With Saes Of Car-t Cells Therapymentioning

confidence: 99%

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors

2022

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Chimeric antigen receptor T (CAR-T) cells technology has been successfully used in the treatment of B cell-derived hematological tumors and multiple myeloma. CAR-T cells are also being studied in a variety of solid tumors. Current clinical reports on CAR-T cells in the treatment of malignant tumors are abundant. The tumor-killing activity of CAR-T cells and the unique adverse effects of CAR-T cells have been confirmed by many studies. There is evidence that serious adverse events can be life-threatening. CAR-T cells therapy is increasingly used in clinical settings, so it is important to pay attention to its serious adverse events. In this review, we summarized the serious adverse events of CAR-T cells in the treatment of malignant tumors by reading literature and searching relevant clinical studies, and discussed the management and treatment of serious adverse events in an effort to provide theoretical support for clinicians who deal with such patients.

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Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Therapy and Coagulopathies

Tang,

Li,

Wang

2024

Interdisciplinary Cancer Research

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

Abstract: Strategies for reducing CRS in CAR-T cells capitalize on the specificity between CAR-T cells, cytokines, and their receptors, the role of macrophages in cytokine release, and genetic constructs to ablate CAR-T function reversibly and irreversibly.

Cited by 8 publications

References 129 publications

Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy

Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy

Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors

Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Therapy and Coagulopathies

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