Cytokine release syndrome

Abstract

During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS). This review provides a comprehensive overview of the mechanisms underlying CRS pathophysiology, risk factors, clinical presentation, differential diagnoses, and prognostic factors. In addition, based on the current evidence we give practical guidance to the management of the cytokine release syndrome.

Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?

“…As mentioned earlier, CRS is the most severe adverse effect induced by CAR T cell 177 therapy, with an incidence of 50-100% [41]. It is believed that binding of the CAR T 178 cell receptor to its antigen induces the activation of bystander cells to release massive 179 amounts of interferon γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which further 180 activate innate immune cells, including macrophages and endothelial cells, to secrete 181 IL-6 and other inflammatory mediators [42]. IL-6 is a central mediator of toxicity in 182 CRS, and its level correlates with the severity of CAR T cell-induced CRS [12,43].…”

Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status

“…Biopharma is developed TJM2, a neutralizing antibody, as a treatment for cytokine release syndrome common in patients suffering from a severe infection of SARS-CoV-2. TJM2 targets the human granulocyte-macrophage colony stimulating factor (GM-CSF), which is responsible for acute and chronic inflammation [78]. TZLS-501 is developed by Tiziana Life Sciences as a monoclonal antibody to treat COVID-19.…”

Bispecific Antibodies in the Treatment of Hematologic Malignancies

“…With the increasing use of T‐cell–engaging immunotherapies, it is paramount that specialists who are dosing patients with these agents should be knowledgeable about the presentation and complications that CRS may cause and its clinical management. However, as these therapies are relatively new, the optimal management of patients is evolving, and requires collaboration between areas of expertise such as radiology, hematology/oncology, critical care, and neurology . Although increases in cytokines are seen in many patients, the magnitude of elevation may not correspond with the clinical response to immunotherapy, and CRS does not appear to be required for a response to T‐cell–redirecting immunotherapies .…”

“…However, as these therapies are relatively new, the optimal management of patients is evolving, and requires collaboration between areas of expertise such as radiology, hematology/oncology, critical care, and neurology . Although increases in cytokines are seen in many patients, the magnitude of elevation may not correspond with the clinical response to immunotherapy, and CRS does not appear to be required for a response to T‐cell–redirecting immunotherapies . Advances in the identification of biomarkers for predicting CRS will aid clinical management of CRS and may equip physicians with agents to treat CRS while maintaining the beneficial activity of the immunotherapy .…”