RARE DISEASE
CAR T cell therapy-associated cytokine release syndrome
CAR T cell therapy-associated cytokine release syndrome
CAR T cell therapy-associated cytokine release syndrome
Synonyms: CAR T cell therapy-associated CRS, Chimeric antigen receptor-T cell therapy-associated cytokine release syndrome
Synonyms: CAR T cell therapy-associated CRS, Chimeric antigen receptor-T cell therapy-associated cytokine release syndrome
Synonyms: CAR T cell therapy-associated CRS, Chimeric antigen receptor-T cell therapy-associated cytokine release syndrome
Drug discovery
1
drug
With orphan designation
Overview
CAR T cell therapy-associated cytokine release syndrome (CRS) is a systemic inflammatory response triggered by rapid immune activation post-infusion, characterized by elevated cytokines (e.g., IL-6, IFN-γ) and clinical manifestations ranging from fever to life-threatening capillary leak syndrome. It occurs in 45-90% of patients, typically within days of treatment. Management includes IL-6 blockade (tocilizumab) and corticosteroids, with severity-dependent escalation to critical care [1][2][6][12].
Categories: rare systemic and rheumatological diseases
Research Papers
146 drug discovery papers related to CAR T cell therapy-associated cytokine release syndrome, with 3 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
146 drug discovery papers related to CAR T cell therapy-associated cytokine release syndrome, with 3 first-in-class and 2 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-05-05 | Extracorporeal blood purification in the management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome following chimeric antigen receptor T cell therapy: a case report
Chimeric antigen receptor T-cell (CAR-T) therapy is associated with potentially severe toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We report a case of a 32-year-old man with refractory diffuse large B-cell lymphoma who developed severe ICANS after axicabtagene ciloleucel infusion despite standard treatment with corticosteroids, tocilizumab, anakinra, and supportive therapy. Because of rapid clinical deterioration, extracorporeal blood purification with CytoSorb was initiated. The treatment was followed by rapid neurological and hemodynamic improvement, reduction of inflammatory markers, and transfer from the intensive care unit to the hematology ward. CAR-T cell expansion, monitored by droplet digital PCR, was preserved after cytokine adsorption. This case suggests that extracorporeal blood purification may be a feasible rescue strategy for severe CAR-T-related neurotoxicity without compromising CAR-T cell activity.
2026-03-27 | Th17-driven CD8+ T cells in hUC-MSC and CAR T-cell dual immunotherapy for superior anti-tumor efficacy
Abstract Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for hematological malignancies; however, its efficacy and safety remain challenging, particularly in the context of high tumor burden. High tumor load and substantial residual lesions significantly impair CAR T-cell function and exacerbate cytokine release syndrome (CRS). Here, we report the development of a novel dual cellular immunotherapy in which human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are co-administered with CD19 CAR T-cells. We demonstrated that this combination therapy enhances the anti-tumor efficacy of CD19 CAR T-cells under high tumor burden condition. In xenograft models of high tumor burden B-cell lymphoma, the dual cellular immunotherapy improved survival, mitigated myelosuppression, and preserved CAR T-cell expansion. Transcriptomic analysis of CAR T-cells revealed enrichment of the Th17 pathway in CAR T-cells, while single-cell RNA sequencing showed enhanced, particularly that of NK-like cytotoxic T lymphocytes characteristics which are associated with Th17 differentiation. Furthermore, in a CRS model, hUC-MSCs attenuate CRS severity by suppressing macrophage activity. Collectively, hUC-MSCs significantly enhance the anti-tumor capability of CD19 CAR T-cells under high tumor burden conditions by inducing CD8 + NK-like cytotoxic T lymphocytes through Th17 differentiation, while concurrently mitigating treatment-related side effects. Our study provides a novel therapeutic strategy to improve clinical outcomes in hematological malignancies.
2026-03-12 | The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy
Chimeric antigen receptor T (CAR T)-cell therapy is revolutionizing cancer treatment in hematologic malignancies, but challenges related to the tumor microenvironment have hindered CAR T success, especially in solid tumors. Myeloid cells in particular have been implicated in CAR T efficacy. In this review, we discuss the roles of myeloid cells in CAR T-associated toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, along with strategies to treat these toxicities by modulating myeloid cells. The review also explores myeloid cell-mediated suppression or enhancement of CAR T function. Finally, strategies used to target myeloid cells in combination with CAR T-cell therapy will be investigated.
2026-05-05 | Extracorporeal blood purification in the management of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome following chimeric antigen receptor T cell therapy: a case report
Chimeric antigen receptor T-cell (CAR-T) therapy is associated with potentially severe toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We report a case of a 32-year-old man with refractory diffuse large B-cell lymphoma who developed severe ICANS after axicabtagene ciloleucel infusion despite standard treatment with corticosteroids, tocilizumab, anakinra, and supportive therapy. Because of rapid clinical deterioration, extracorporeal blood purification with CytoSorb was initiated. The treatment was followed by rapid neurological and hemodynamic improvement, reduction of inflammatory markers, and transfer from the intensive care unit to the hematology ward. CAR-T cell expansion, monitored by droplet digital PCR, was preserved after cytokine adsorption. This case suggests that extracorporeal blood purification may be a feasible rescue strategy for severe CAR-T-related neurotoxicity without compromising CAR-T cell activity.
2026-03-27 | Th17-driven CD8+ T cells in hUC-MSC and CAR T-cell dual immunotherapy for superior anti-tumor efficacy
Abstract Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for hematological malignancies; however, its efficacy and safety remain challenging, particularly in the context of high tumor burden. High tumor load and substantial residual lesions significantly impair CAR T-cell function and exacerbate cytokine release syndrome (CRS). Here, we report the development of a novel dual cellular immunotherapy in which human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are co-administered with CD19 CAR T-cells. We demonstrated that this combination therapy enhances the anti-tumor efficacy of CD19 CAR T-cells under high tumor burden condition. In xenograft models of high tumor burden B-cell lymphoma, the dual cellular immunotherapy improved survival, mitigated myelosuppression, and preserved CAR T-cell expansion. Transcriptomic analysis of CAR T-cells revealed enrichment of the Th17 pathway in CAR T-cells, while single-cell RNA sequencing showed enhanced, particularly that of NK-like cytotoxic T lymphocytes characteristics which are associated with Th17 differentiation. Furthermore, in a CRS model, hUC-MSCs attenuate CRS severity by suppressing macrophage activity. Collectively, hUC-MSCs significantly enhance the anti-tumor capability of CD19 CAR T-cells under high tumor burden conditions by inducing CD8 + NK-like cytotoxic T lymphocytes through Th17 differentiation, while concurrently mitigating treatment-related side effects. Our study provides a novel therapeutic strategy to improve clinical outcomes in hematological malignancies.
2026-03-12 | The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy
Chimeric antigen receptor T (CAR T)-cell therapy is revolutionizing cancer treatment in hematologic malignancies, but challenges related to the tumor microenvironment have hindered CAR T success, especially in solid tumors. Myeloid cells in particular have been implicated in CAR T efficacy. In this review, we discuss the roles of myeloid cells in CAR T-associated toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, along with strategies to treat these toxicities by modulating myeloid cells. The review also explores myeloid cell-mediated suppression or enhancement of CAR T function. Finally, strategies used to target myeloid cells in combination with CAR T-cell therapy will be investigated.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for CAR T cell therapy-associated cytokine release syndrome, including 1 approved therapy.
1 orphan drug designation for CAR T cell therapy-associated cytokine release syndrome, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
tocilizumab [Actemra] | antibodies | FDA | 2017-08-01 | 2017-08-30 | Genentech Inc., a member of the Roche Group |
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