Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies

Freyer, Craig W.; Porter, David L.

doi:10.1016/j.jaci.2020.07.025

Cited by 216CAR-T cell therapy researchAutoimmune and Inflammatory Disorders ResearchCancer Immunotherapy and Biomarkers

Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies

Open access

Freyer, Craig W., Porter, David L.·2020·Journal of Allergy and Clinical Immunology

DOI 10.1016/j.jaci.2020.07.025

Open this paper in CoChat — free account Open PDF

Abstract

Chimeric antigen receptor T cells are a new and exciting immunotherapeutic approach to managing cancer, with impressive efficacy but potentially life-threatening inflammatory toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with severe CRS may develop capillary leak syndrome and disseminated intravascular coagulation, with a cytokine signature similar to that of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Moderate-to-severe CRS is managed with the IL-6 receptor antagonist tocilizumab with or without corticosteroids, with questions remaining regarding the optimal management of nonresponders. ICANS is an inflammatory neurotoxicity typically occurring after CRS and characterized by impaired blood-brain barrier integrity. Symptoms of encephalopathy range from mild confusion and aphasia to somnolence, obtundation, and in some cases seizures and cerebral edema. ICANS is currently managed with corticosteroids; however, the optimal dose and duration remain to be determined. Little information is available to guide the management of patients with steroid-refractory ICANS. Numerous cytokine-targeted therapies have been proposed to manage these inflammatory toxicities, but few clinical data are available. Management of inflammatory toxicities of chimeric antigen receptor T cells often requires multidisciplinary management and intensive care, during which allergists and immunologists may…

Integrity signals

Registry

Crossref · 10.1016/j.jaci.2020.07.025

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

CRS and ICANS affect approximately 45% to 50% of patients, with severe conditions (grade ≥ 3) occurring in 10% to 12% of patients.
“Two of the most common complications are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which affect approximately 45% to 50% of patients, with severe conditions (grade ≥ 3) occurring in 10% to 12% of patients.”
From The burdens, coping strategies, and unmet needs of family caregivers of Chinese patients with lymphoma receiving commercial CAR-T-cell therapy: A qualitative study (2026) · cites this paper as [9]

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413 · see citing works
Self-citation
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Schuster, S. J., Bishop, M. R., Tam, C. S., Waller, E. K., Borchmann, P., McGuirk, J. P., Jäger, U., Jaglowski, S., Andreadis, C., Westin, J. R., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1804980 · Cited by 4,112 · see citing works
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial
Lee, D. W., Kochenderfer, J. N., Stetler-Stevenson, M., Cui, Y. K., Delbrook, C., Feldman, S. A., Fry, T. J., Orentas, R., Sabatino, M., Shah, N. N., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61403-3 · Cited by 2,898 · see citing works
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709919 · Cited by 2,688 · see citing works
Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia
Teachey, D. T., Lacey, S. F., Shaw, P. A., Melenhorst, J. J., Maude, S. L., Frey, N., Pequignot, E., Gonzalez, V. E., Chen, F., Finklestein, J., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0040 · Cited by 1,102 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B‐cell lymphoma
Oluwole, O. O., Bouabdallah, K., Muñoz, J., de Guibert, S., Vose, J., Bartlett, N., Lin, Y., Deol, A., Mcsweeney, P., Goy, A., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17527 · Cited by 198
“Hypophosphataemia 11 (28) 6 (15) 0 Thrombocytopenia 10 (25) 5 (13) 2 (5) Tremor 9 (23) 1 (3) 0”
Emerging Targeted Therapies for HER2-Positive Breast Cancer
Mercogliano, M. F., Bruni, S., Mauro, F. L., & Schillaci, R. (2023) · Cancers · doi:10.3390/cancers15071987 · Cited by 203 · see citing works
Cancer immunotherapy: Challenges and limitations
Taefehshokr, S., Parhizkar, A., Hayati, S., Mousapour, M., Mahmoudpour, A., Eid, L. E., Rahmanpour, D., Fattahi, S., Shabani, H., & Taefehshokr, N. (2021) · Pathology - Research and Practice · doi:10.1016/j.prp.2021.153723 · Cited by 198 · see citing works
Immunotherapy in hematologic malignancies: achievements, challenges and future prospects
Tang, L., Huang, Z., Mei, H., & Hu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01521-5 · Cited by 171 · see citing works
“555 CAR-T therapy-related toxicities Cytokine Release Syndrome (CRS) and neurotoxicity are the most common and unique toxicities associated with CAR T-cell therapies, 556 – 567 and they are completely different from the irAEs that are associated with the treatment of ICIs.”
Background
Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond
Nguyen, S. M. T., Rupprecht, C. P., Haque, A., Pattanaik, D., Yusin, J. S., & Krishnaswamy, G. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22157785 · Cited by 176 · see citing works
“The onset of CRS is usually 2 to 3 days after infusion of medications, with flu-like symptoms (fever, anorexia, myalgia, headaches, rigor, malaise) followed by either spontaneous resolution or progression to multisystem involvement with hypotension, capillary leak, pneumonitis, hypoxemia, renal insufficiency and disse…”
Background
The multifaceted roles of GSDME-mediated pyroptosis in cancer: therapeutic strategies and persisting obstacles
Hu, Y., Liu, Y., Zong, L., Zhang, W., Liu, R., Xing, Q., Liu, Z., Yan, Q., Li, W., Lei, H., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06382-y · Cited by 127 · see citing works
“Importantly, pyroptosis-related factors including IL-1 β and IL-6 released by macrophages play a signi ﬁ cant role in CRS-related in ﬂ ammatory responses [185, 186].”
Background
Reactions Related to CAR-T Cell Therapy
Miao, L., Zhang, Z., Ren, Z., & Li, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.663201 · Cited by 124 · see citing works
“(46) reports that detection of CRS is done through clinical diagnosis, and inflammatory cytokine profiles are useful in confirmatory tests; however, these data are not used to determine the grade or treatment of CRS.”
Method
Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions
Zhong, Y., & Liu, J. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02077-1 · Cited by 116 · see citing works
“Treatment for alleviating CRS includes the administration of tocilizumab (an IL-6 receptor antagonist) and corticosteroids, which can be effective but may also dampen the antitumor effects of the CAR-T cells [30].”
Background
Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer
Zheng, W., Zhu, T., Tang, L., Li, Z., Jiang, G., & Huang, X. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04206-3 · Cited by 113 · see citing works
“Additionally, in contrast to the excessive inflammatory response of CAR-T cells [58], their derived exosomes may be administered quantitatively.”
Background
Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms
Wu, Y., Sun, X., Kang, K., Yang, Y., Li, H., Zhao, A., & Niu, T. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01621-x · Cited by 113 · see citing works
In-Vivo Induced CAR-T Cell for the Potential Breakthrough to Overcome the Barriers of Current CAR-T Cell Therapy
Xin, T., Li, C., Zhou, C., Zhao, Y., Hu, Z., & Wu, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.809754 · Cited by 110 · see citing works
Critical care management of chimeric antigen receptor T‐cell therapy recipients
Shimabukuro‐Vornhagen, A., Böll, B., Schellongowski, P., Valade, S., Metaxa, V., Azoulay, É., & von Bergwelt‐Baildon, M. (2021) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21702 · Cited by 78 · see citing works
Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies
Zhang, Y., Qin, D., Shou, A., Liu, Y., Wang, Y., & Zhou, L. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12196124 · Cited by 78 · see citing works
“Patients often show the ﬁrst CRS symptoms 14 days after receiving CAR-T cells; delayed CRS is rarer [22,23].”
Background
Polymer- and lipid-based gene delivery technology for CAR T cell therapy.
Pinto, I., Cordeiro, R. A., & Faneca, H. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.038 · Cited by 72 · see citing works
Suppression of cytokine release syndrome during CAR-T-cell therapy via a subcutaneously injected interleukin-6-adsorbing hydrogel
Li, X., Gong, N., Tian, F., Zhang, S., Zhang, Y., Wang, Y., Qing, G., Wang, Y., Li, F., Xu, Y., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01084-4 · Cited by 74 · see citing works
CAR‐T cell therapy for lung cancer: Potential and perspective
Chen, L., Chen, F., Li, J., Pu, Y., Yang, C., Wang, Y., Lei, Y., & Huang, Y. (2022) · Thoracic Cancer · doi:10.1111/1759-7714.14375 · Cited by 77 · see citing works
“Previous studies have found that the systemic inflammatory response associated with CRS may contribute to the risk of complications CRES.(115,116) In addition, clinical studies have shown that the activation of endothelial cells facilitated the disruption of the blood–brain barrier, allowing immune effector cells and…”
Background
The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions
Li, Y., Ming, Y., Fu, R., Li, C., Wu, Y., Jiang, T., Li, Z., Ni, R., Li, L., Su, H., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.950923 · Cited by 69 · see citing works
“CAR-T manufacturing generally takes 2–4 weeks and may extend to 3–6 weeks due to the turnaround and transportation time to the final infusion into the patient (Freyer and Porter, 2020).”
Background
Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma
Wu, J., Meng, F., Cao, Y., Zhang, Y., Zhu, X., Wang, N., Wang, J., Huang, L., Zhou, J., & Xiao, Y. (2021) · Blood Cancer Journal · doi:10.1038/s41408-021-00523-2 · Cited by 66 · see citing works
Hallmarks of immune response in COVID-19: Exploring dysregulation and exhaustion
Mazzoni, A., Salvati, L., Maggi, L., Annunziato, F., & Cosmi, L. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101508 · Cited by 65 · see citing works
CAR T-Cell therapy for the management of mantle cell lymphoma
Huang, Z., Chavda, V. P., Bezbaruah, R., Dhamne, H., Yang, D., & Zhao, H.-B. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01755-5 · Cited by 56 · see citing works
“Severe toxicities like cytokine storm, macrophage activation syndrome, neurotoxicity, and HLH in patients due to the CAR T-cell therapy are some other unavoidable obstacles [160].”
Background
CAR-T cell therapy: Where are we now, and where are we heading?
Wang, J., & Wang, L. (2023) · Blood Science · doi:10.1097/bs9.0000000000000173 · Cited by 63 · see citing works
“57 Early manifestations may include expressive aphasia and changes in writing, followed by progression to altered levels of consciousness, coma, seizures, weakness, and cerebral edema.”
Background
THE INTERNATIONAL PROGNOSTIC INDEX IS ASSOCIATED WITH OUTCOMES IN DIFFUSE LARGE B CELL LYMPHOMA AFTER CAR T CELL THERAPY
Garcia-recio, M., Wudhikarn, K., Pennisi, M., Alonso-Trillo, R., Flynn, J., Shouval, R., Afuye, A., Silverberg, M. L., Batlevi, C., Dahi, P., et al. (2020) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2020.10.022 · Cited by 46 · see citing works
Advances in CAR‐Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies
Chen, Z., Hu, Y., & Mei, H. (2023) · Advanced Science · doi:10.1002/advs.202303215 · Cited by 43 · see citing works
Immunotherapies of acute myeloid leukemia: Rationale, clinical evidence and perspective
Wu, Y., Li, Y., Gao, Y., Zhang, P., Jing, Q., Zhang, Y., Jin, W., Wang, Y., Du, J., & Wu, G. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116132 · Cited by 35 · see citing works
Comparison of CAR T-cell and bispecific antibody as third-line or later-line treatments for multiple myeloma: a meta-analysis
Liang, X.-J., Wang, Y.-F., Luo, B.-W., Lin, B., Lu, W.-X., Tian, S., Liu, D., & Wang, L. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010064 · Cited by 37 · see citing works
Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies
Huang, Y., Qin, Y., He, Y., Qiu, D., Zheng, Y., Wei, J., Zhang, L., Yang, D., & Li, Y. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101082 · Cited by 39 · see citing works
New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies
Yang, Y., Peng, H., Wang, J., & Li, F. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00573-9 · Cited by 32 · see citing works
Late relapse after CAR-T cell therapy for adult patients with hematologic malignancies: A definite evidence from systematic review and meta-analysis on individual data
Zinzi, A., Gaio, M., Liguori, V., Cagnotta, C., Paolino, D., Paolisso, G., Castaldo, G., Nicoletti, G. F., Rossi, F., Capuano, A., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106742 · Cited by 33 · see citing works
Alternative CAR Therapies: Recent Approaches in Engineering Chimeric Antigen Receptor Immune Cells to Combat Cancer
Moreno, C. M., Haynie, C., Cheever, A., & Weber, K. S. (2022) · Biomedicines · doi:10.3390/biomedicines10071493 · Cited by 37 · see citing works
“CRS is one of the biggest drawbacks of CAR T cell therapy and can lead to rapid death [42,43].”
Background
Dramatic Response to Anti-IL-6 Receptor Therapy in Children With Life-Threatening Myelin Oligodendrocyte Glycoprotein-Associated Disease
McLendon, L., Gambrah-Lyles, C., Viaene, A., Fainberg, N. A., Landzberg, E., Tucker, A. M., Madsen, P. J., Huh, J. W., Silver, M. R., Arena, J. D., et al. (2023) · Neurology: Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000200150 · Cited by 33
“13 Tocilizumab is not believed to cross the BBB, 16 would not be able to mitigate IL-6 binding in the CNS, and, conceptually, could worsen cerebral symptoms in MOGAD.”
Background
Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9
Amiri, M., Moaveni, A. K., Zolbin, M. M., Shademan, B., & Nourazarian, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1462697 · Cited by 35 · see citing works
“ICANS rarely occurs without preceding CRS, and when it does, it tends to be mild (65).”
Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome
Chen, P., Tang, Y., He, W., Yang, R., Lan, Z., Chen, R., & Zhang, P. (2022) · Mediators of Inflammation · doi:10.1155/2022/7137900 · Cited by 39 · see citing works
“Clinical studies have shown that increased blood–brain barrier (BBB) permeability can be observed in sufferers with neurological symptoms of CRS [69].”
Background
Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy
Xie, X., Zhang, J., Wang, Y., Shi, W., Tang, R., Tang, Q., Sun, S., Wu, R., Xu, S., Wang, M., et al. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100926 · Cited by 26 · see citing works
“In addition, CAR-T therapy causes cytokines release syndrome, while TILs cause capillary leak syndrome, which limits their further application [78].”
Background
Chimeric antigen receptor-T cell therapy-related cardiotoxicity in adults and children cancer patients: A clinical appraisal
Camilli, M., Maggio, L., Tinti, L., Lamendola, P., Lanza, G. A., Crea, F., & Lombardo, A. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1090103 · Cited by 29 · see citing works
“, adrenaline, noradrenaline, vasopressin) should be considered (26, 55, 56).”
Engineering CAR-NK cells targeting CD33 with concomitant extracellular secretion of anti-CD16 antibody revealed superior antitumor effects toward myeloid leukemia
Zhang, R., Liu, Q.-X., Zhou, S., He, H., Zhao, M.-F., & Ma, W.-J. (2022) · bioRxiv · doi:10.1101/2022.11.14.516308 · Cited by 27
“However, CAR-T therapy is also facing many challenges such as treatment-related severe toxicity and side effects, including cytokine release syndrome (CRS) and neurotoxicity [6,7].”
Background
Precision sniper for solid tumors: CAR-NK cell therapy
Li, S., Jing, J., Chen, Y., Chi, E., Wang, B., Xie, Z., Yang, W., Shen, H., & Pan, J. (2025) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-025-04106-z · Cited by 18 · see citing works
“…cytokine release syndrome (CRS), which can result in complications such as capillary leak syndrome (CLS), disseminated intravascular coagulation (DIC) and even immune effector cell-associated neurotoxicity syndrome (ICANS), thereby limiting the clinical application of CAR-T cell therapy [114].”
Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model
Tachi, T., Kijima, N., Kuroda, H., Ikeda, S., Murakami, K., Nakagawa, T., Yaga, M., Nakagawa, K., Utsugi, R., Hirayama, R., et al. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-024-03808-0 · Cited by 28 · see citing works
“Unlike T cells, natural killer (NK) cells do not induce graft-versus-host disease (GVHD) when infused into allogeneic donors and are not associated with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, which are adverse effects of CAR-T cell therapy [16, 17].”
Background
CAR-T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap
Gatto, L., Ricciotti, I., Tosoni, A., di Nunno, V., Bartolini, S., Ranieri, L., & Franceschi, E. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1206983 · Cited by 24 · see citing works
“It is likely that the systemic inflammatory response associated with CRS underpins the development of neurotoxicity (20, 21).”
Background
Mesenchymal stem cell suppresses the efficacy of CAR-T toward killing lymphoma cells by modulating the microenvironment through stanniocalcin-1
Zhang, R., Liu, Q.-X., Zhou, S., He, H., Zhao, M.-F., & Ma, W.-J. (2022) · bioRxiv · doi:10.7554/elife.82934 · Cited by 24 · see citing works
“In spite of the striking achievements, CAR-T therapy are also facing many challenges such as the treatment-related severe toxicity and side effects, including cytokine release syndrome (CRS) and neurotoxicity [3,4].”
Background
Pathogenesis, Diagnosis, and Management of Cytokine Release Syndrome in Patients with Cancer: Focus on Infectious Disease Considerations
Arvanitis, P., Tziotis, A., Papadimatos, S., & Farmakiotis, D. (2025) · Current Oncology · doi:10.3390/curroncol32040198 · Cited by 22 · see citing works
“…to counter the inflammatory response, as well as immune suppression from prior treatment lines, particularly with CAR T-cell therapy, amplifies patient vulnerability to secondary infections, which may mimic or exacerbate CRS and ICANS, creating diagnostic and therapeutic challenges [2,35].”
Influential
Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy
Song, Z., Tu, D.-Y., Tang, G., Liu, N., Tai, Z.-G., Yang, J.-M., & Wang, Y. (2023) · Haematologica · doi:10.3324/haematol.2022.281455 · Cited by 22 · see citing works
“Age in years, median (IQR) 31 (15-62) 59 (49-66) 20 (12-54)”
Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma
Pu, J., Liu, T., Sharma, A., Jiang, L., Wei, F., Ren, X., Schmidt‐Wolf, I. G. H., & Hou, J. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00576-6 · Cited by 22 · see citing works
A new clinical age of aging research
Zhang, Z., Yang, R., Zi, Z., & Liu, B. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.08.004 · Cited by 25 · see citing works
Collapsing Focal Segmental Glomerulosclerosis and Acute Kidney Injury Associated With Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: A Case Report
Acharya, R., Horn, B., Zeng, X., & Upadhyay, K. (2021) · Kidney Medicine · doi:10.1016/j.xkme.2021.06.011 · Cited by 21
“The risk for and severity of cytokine release syndrome increase with greater disease burden and higher CAR-T dose.(7) Less commonly, AKI can occur secondary to cytokine-induced vasodilation, decreased cardiac output, increased vascular permeability, and third spacing of fluids leading to intravascular volume depletion.”
Background
Intrathecal Chemotherapy as a Potential Treatment for Steroid-refractory Immune Effector Cell-associated Neurotoxicity Syndrome
Asawa, P., Vusqa, U., Khan, C., Samhouri, Y., & Fazal, S. (2022) · Anticancer Research · doi:10.21873/anticanres.15876 · Cited by 20
Current Challenges in Chimeric Antigen Receptor T-cell Therapy in Patients With B-cell Lymphoid Malignancies
Kim, S. J., Yoon, S. E., & Kim, W. S. (2024) · Annals of Laboratory Medicine · doi:10.3343/alm.2023.0388 · Cited by 17 · see citing works
“Although ICANS can occur without an event of preceding CRS, most cases of ICANS occur following CRS, and its severity is related to the degree of CRS [34, 35].”
Background
Strategies for Reducing Toxicity and Enhancing Efficacy of Chimeric Antigen Receptor T Cell Therapy in Hematological Malignancies
Wang, H., Tang, L. Y., Kong, Y., Liu, W., Zhu, X., & You, Y. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119115 · Cited by 19 · see citing works
Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A Review of What We Know So Far
Gilkeson, G. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42081 · Cited by 19 · see citing works
“The other more important downside is the cytokine release syndrome that develops in many patients (4).”
Background
Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies
Wang, X. W., He, X., Zhang, T., Liu, J., & Zhao, M. (2025) · Annals of Hematology · doi:10.1007/s00277-025-06467-y · Cited by 20 · see citing works
“Research has shown that preventive use of corticosteroids can reduce the incidence and mortality of CRS, ICANS, and HLH [15, 18, 101].”
Nanomaterial-based cancer immunotherapy: enhancing treatment strategies
Tian, M., Liu, X., & Pei, H. (2024) · Frontiers in Chemistry · doi:10.3389/fchem.2024.1492215 · Cited by 18 · see citing works
“…despite its remarkable ef ﬁ cacy in certain hematologic malignancies, CAR-T cell therapy is associated with severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity, which can lead to serious complications and even life-threatening conditions (Freyer and Porter, 2020).”
Background
NK/DC crosstalk-modulating antitumor activity via Sema3E/PlexinD1 axis for enhanced cancer immunotherapy
Ali, A., Alamri, A., & Hajar, A. (2024) · Immunologic research · doi:10.1007/s12026-024-09536-y · Cited by 17 · see citing works
Nanotechnology in Advancing Chimeric Antigen Receptor T Cell Therapy for Cancer Treatment
Kang, X., Mita, N., Zhou, L., Wu, S., Yue, Z., Babu, R. J., & Chen, P. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16091228 · Cited by 19 · see citing works
“Fever is usually the initial symptom of cytokine release syndrome after CAR-T cell infusion, appearing from a few hours after to over a week later [152].”
Background
Ganoderic acid T, a novel activator of pyruvate carboxylase, exhibits potent anti-liver cancer activity.
Lei, B., Zhang, M.-J., Shi, X.-L., Feng, N., Yin, J., Dong, R., Xie, C.-M., Zhu, Y., Zhong, J.-J., & Ni, B. (2025) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2025.156321 · Cited by 16 · see citing works
Cell-based immunotherapies for solid tumors: advances, challenges, and future directions
Zhao, T., You, J., Wang, C., Li, B., Liu, Y., Shao, M., Zhao, W., & Zhou, C. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1551583 · Cited by 15 · see citing works
“The reduced risk of CRS/ICANS with CAR-NK therapy makes it an attractive option, particularly for patients who may be at high risk for these toxicities with CAR-T cells (77).”
Influential
Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma
Pawlowski, K. D., Duffy, J., Gottschalk, S., & Balyasnikova, I. (2023) · Cancers · doi:10.3390/cancers15245852 · Cited by 16 · see citing works
“ICANS is managed with supportive care, corticosteroids, or the IL-1 receptor antagonist, anakinra [59,61].”
Background
CAR T‐Cell Therapy for Multiple Myeloma: A Clinical Practice‐Oriented Review
Sadek, N. L., Costa, B. A., Nath, K., & Mailankody, S. (2023) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3057 · Cited by 13 · see citing works
“44,54 CRS incidence was more pronounced in ide-cel patients with a higher baseline ferritin, but this association was not seen in cilta-cel.”
Background
Bispecific NK-cell engager targeting BCMA elicits stronger antitumor effects and produces less proinflammatory cytokines than T-cell engager
Xiao, X., Cheng, Y., Zheng, X.-D., Fang, Y.-H., Zhang, Y., Sun, R., Tian, Z., & Sun, H.-Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1113303 · Cited by 15 · see citing works
“Frontiers in Immunology 10 lead to cytokine release syndrome (40, 41).”
Background
Designing immunity with cytokines: A logic-based framework for programmable CAR therapies.
Upadhyay, S., Upmanyu, K., & Gabr, M. (2025) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2025.09.004 · Cited by 14 · see citing works
Mitigation and Management of Common Toxicities Associated with the Administration of CAR-T Therapies in Oncology Patients
Renninger, J. P., Kurz, L., & Stein, H. (2025) · Drug Safety · doi:10.1007/s40264-025-01538-5 · Cited by 13 · see citing works
Cardiovascular Toxicity of Antineoplastic Treatments in Hematological Diseases: Focus on Molecular Mechanisms to Improve Therapeutic Management
Barachini, S., Buda, G., & Petrini, I. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13061574 · Cited by 12 · see citing works
“Primarily indicated for juvenile idiopathic arthritis and rheumatoid arthritis, tocilizumab’s efficacy in managing severe CRS was also demonstrated in landmark studies that investigated CAR T-cell therapy [237,238].”
Background
Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials
Wang, X., Zhao, A., Zhu, J., & Niu, T. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1348955 · Cited by 14 · see citing works
“In addition, tocilizumab was highly effective and widely used for treating CRS and ICANS (17, 27, 37, 38).”
Method
Immunotherapy of Multiple Myeloma: Promise and Challenges
Abramson, H. N. (2021) · ImmunoTargets and Therapy · doi:10.2147/itt.s306103 · Cited by 19 · see citing works
CAR-exosomes derived from immune cells: an emerging nanoscale vanguard in overcoming tumor immunotherapy hurdles
Zhao, X., Zhao, B., Sun, Y., & Liu, A.-G. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1655095 · Cited by 13 · see citing works
“These include severe on-target off-tumor toxicities such as cytokine release syndrome (CRS) and neurotoxicity (3, 4), as well as physical barriers and immunosuppressive characteristics within the tumor microenvironment (TME) that impede suf ﬁ cient CAR-T cell in ﬁ ltration and activation (5).”
Comparing the Differences in Adverse Events among Chimeric Antigen Receptor T-Cell Therapies: A Real-World Pharmacovigilance Study
Guo, Z.-H., Ding, Y., Wang, M., Zhai, Q., Liu, J.-Y., & Du, Q. (2024) · Pharmaceuticals · doi:10.3390/ph17081025 · Cited by 13 · see citing works
“Since the FAERS database records AE names using the preferred terms (PT) terminology of the Medical Dictionary for Regulatory Activities (MedDRA), and the MedDRA is updated every March and September, involving adjustments to PT levels and changes to system organ classes (SOCs), the latest version of the MedDRA was use…”
BackgroundMethodInfluential
Chimeric antigen receptor natural killer cells: a promising antitumor immunotherapy
Wang, Y., Jin, S., Zhuang, Q., Liu, N., Chen, R., Adam, S. A., Jin, J., & Sun, J. (2023) · MedComm · doi:10.1002/mco2.422 · Cited by 14 · see citing works
“17 Compared with CAR T cells, CAR-NK cells are less likely to induce CRS and neurotoxicity due to a shorter lifespan and a cytokine secretion spectrum different from that of T cells.”
Background
Multi-centers experience using therapeutic plasma exchange for corticosteroid/tocilizumab-refractory cytokine release syndrome following CAR-T therapy.
Pu, Y., Zhao, Y., Qi, Y.-K., Liu, Y., Zhang, M., Xiao, X., Lyu, H., Meng, J.-X., Zhu, H.-B., Xu, K.-L., et al. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.111761 · Cited by 11 · see citing works
Chimeric antigen receptor T-cell therapy-induced nervous system toxicity: a real-world study based on the FDA Adverse Event Reporting System database
Ren, X., Zhang, G., Li, G., & Wang, Y. (2024) · BMC Cancer · doi:10.1186/s12885-023-11753-x · Cited by 13 · see citing works
“The pathogenesis of ICANS is not completely understood, but it appears to be related to cytokine-induced toxicity rather than a non-tumor effect on the target [12].”
BackgroundInfluential
The Immune Microenvironment: New Therapeutic Implications in Organ Fibrosis
Chen, X., Wu, C. F., Tang, F., Zhou, J., Mo, L., Li, Y., & He, J. (2025) · Advanced Science · doi:10.1002/advs.202505067 · Cited by 8 · see citing works
Pathomechanism of Adverse Reactions to Biological Treatment of Inflammatory Skin Conditions
Li, L.-C., Naisbitt, D., Sun, Y.-H., & Zhang, F.-R. (2024) · Clinical and Experimental Allergy · doi:10.1111/cea.14583 · Cited by 10 · see citing works
Safe and potent anti‐CD19 CAR T‐cells with shRNA‐IL‐6 gene silencing element in patients with refractory or relapsed B‐cell acute lymphoblastic leukemia
Ma, J.-F., Yan, J.-W., Liu, M.-J., Yan, C.-L., Tang, X.-W., Qiu, H.-Y., Miao, M., Han, Y., Li, L., Kang, L.-Q., et al. (2024) · HemaSphere · doi:10.1002/hem3.70007 · Cited by 10 · see citing works
Current status and future prospects of chimeric antigen receptor-T cell therapy in lymphoma research: A bibliometric analysis
Ou, L., Su, C., Liang, L., Duan, Q., Li, Y., Zang, H., He, Y., Zeng, R., Li, Y., Zhou, H. H., et al. (2023) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2023.2267865 · Cited by 9 · see citing works
“69,70 To effectively prevent and manage CRS, various methods can be adopted, including the use of drugs, reducing the dose of CAR-T cells, selecting appropriate patients, and early intervention.”
Method
Shear Conditioning Promotes Microvascular Endothelial Barrier Resilience in a Human BBB‐on‐a‐Chip Model of Systemic Inflammation Leading to Astrogliosis
Chen, K., Linares, I. M., Trempel, M. A., Feidler, A. M., De Silva, D., Farajollahi, S., Jones, J., Kuebel, J., Kasap, P., Engelhardt, B., et al. (2025) · Advanced Science · doi:10.1002/advs.202508271 · Cited by 9 · see citing works
Improved CAR internalization and recycling through transmembrane domain optimization reduces CAR-T cytokine release and exhaustion
Xie, S., Long, J., Wang, R., Xiang, R.-F., Xian, H.-J., Wang, Y.-X., Dou, W., Zhang, W.-J., Li, D., Kang, T., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1531344 · Cited by 9 · see citing works
“How to avoid severe CRS is another challenge in CAR-T therapy (3, 4).”
Safety assessment of anti-B cell maturation antigen chimeric antigen receptor T cell therapy: a real-world study based on the FDA adverse event reporting system database
Liu, W., Lin, S., Zhu, X., Yin, L., Liu, Q., Lei, S., & Feng, B. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1433075 · Cited by 8 · see citing works
“For cilta-cel, frequently occurring AEs include CRS (n=158), pyrexia (n=58), and ICANS (n=45).”
BackgroundInfluential
Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting
Guo, R., Lu, W., Zhang, Y., Cao, X., Jin, X. K., & Zhao, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.839097 · Cited by 11 · see citing works
Janus Kinase Inhibitors and Cell Therapy
Assal, A., & Mapara, M. Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.740847 · Cited by 8 · see citing works
“Risk factors suggested for the development of CRS include higher disease burden, higher cell dose infused, lymphodepleting chemotherapy selection, cell product used, a low pre-treatment platelet count, and the CD4/CD8 T cell ratio (16, 17).”
Background
CD19 -targeted CAR T therapy treating hematologic malignancies: hidden danger is the next neighbor to security?
Ye, X.-S., Ge, M., Tan, M., Wu, Y.-Q., Zhang, H.-Q., & Fu, Z.-X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1490491 · Cited by 8 · see citing works
“Currently, the occurrence and severity of CRS are assessed by continuously monitoring patient IL6 levels and the biomarker C-reactive protein (CRP) (18).”
Influential
Unmet needs and lived experience of patients receiving CAR T-cell therapy
O'Shea, P., Johnson, P. C., El-Jawahri, A., & Leblanc, T. W. (2025) · Leukemia and Lymphoma · doi:10.1080/10428194.2025.2455488 · Cited by 8 · see citing works
Interleukin signaling in the regulation of natural killer cells biology in breast cancer
Xu, J., Gao, H., Azhar, M., Xu, H.-F., Chen, S., Li, M., Ni, X., Yan, T., Zhou, H., Long, Q., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1449441 · Cited by 8 · see citing works
“In severe instances, these conditions may result in life-threatening attacks by donor cells on the recipient ’ s tissues (7).”
Background
Optical sensing and control of T cell signaling pathways
Lee, H. N., Lee, S. E., Inn, K.-S., & Seong, J. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2023.1321996 · Cited by 8
“In addition, side effects such as cytokine release syndrome and neurotoxicity may occur due to the hyperactivation of CAR-T cells (Freyer and Porter, 2020; Siegler and Kenderian, 2020).”
Background
The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia
Chen, Z., Xin, Q., Wei, W., & Wu, Y.-J. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16029 · Cited by 8
“…serum IL-2, TNF-α, IFN-γ, IL-8 (CXCL8), IL-10,MCP-1 (CCL2) andMIP-1α (CCL3), and then cytokine release syndrome occurs, which resulted in capillary leak syn- drome, disseminated intravascular coagulation (DIC) and even immune effector cell-related neurotoxicity syndrome (Freyer & Porter, 2020).”
Background
Multiple Myeloma and Precursor Plasma Cell Disorders: From Emerging Driver Mutations to Current and Future Therapeutic Strategies
Sutanto, H., Romadhon, P. Z., Fatmawati, V. R., Waitupu, A., Ansharullah, B. A., Rachma, B., Elisa, E., Pratiwi, L., & Adytia, G. J. (2025) · Hemato · doi:10.3390/hemato6030029 · Cited by 8 · see citing works
Utilizing plasma exchange for severe cytokine release syndrome after CAR-T cell therapy: clinical experience and literature insights
Zhang, J., Xie, D.-L., Tang, M., Gong, Q., Huang, X., Li, J., Xu, S.-N., Luo, N., Sun, H.-L., & Tan, F. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1597512 · Cited by 7
“Despite its impressive clinical ef ﬁ cacy, CAR-T cell therapy is still accompanied with signi ﬁ cant adverse effects, which might restrict its large-scale clinical applications (6, 7).”
Immune Effector Cell-Associated Neurotoxicity Syndrome After CAR T-Cell Therapy and Other Psychiatric Manifestations: A Review and Case Series
Buciuc, A., Tran, S., Weber, M., Padilla, V., Rueda-Lara, M., & Espinel, Z. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14051451 · Cited by 7 · see citing works
Novel chimeric antigen receptor‐expressing T cells targeting the malignant mesothelioma‐specific antigen sialylated HEG1
Kouro, T., Higashijima, N., Horaguchi, S., Mano, Y., Kasajima, R., Xiang, H., Fujimoto, Y., Kishi, H., Hamana, H., Hoshino, D., et al. (2024) · International Journal of Cancer · doi:10.1002/ijc.34843 · Cited by 8 · see citing works
“In addition, CRS could not be evaluated in this model using NSG mice because CRS has been reported to be caused by cytokines released from macrophages/monocytes stimulated by overactivated CAR-T cells, 38 but NSG mice have defective macrophage/monocyte functions.”
Method
CAR cell design strategies in solid tumors.
Wang, L., Chen, X., Zhang, L., Niu, B.-N., Li, L., Sun, Y., & Yuan, X.-L. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109345 · Cited by 7 · see citing works
Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions
Rizkallah, J., Wehbeh, B. E. D., Wassouf, W., Salameh, E., Joumaa, A., Haddad, F. J., Hamade, L., Charbel, N., Bakri, G. M., Awada, A., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1800292 · Cited by 6 · see citing works
Cytokine‐Engineered Chimeric Antigen Receptor‐T Cell Therapy: How to Balance the Efficacy and Toxicity
Zhang, X., Aimaiti, G., Guan, Y., Sha, Y.-Z., Zhou, W., Shen, J.-F., Zhao, B., & Yuan, W.-E. (2026) · Advancement of science · doi:10.1002/advs.202518547 · Cited by 6 · see citing works
Photocontrolled trimethoprim PROTACs targeting the eDHFR protein tag
Sharma, N., Sarkar, S., Ko, T., Edwards, K. J., Pham, J. M., Nguyen, T., Gong, A. Z., Flores, J. I., Trauner, D. H., & Sellmyer, M. A. (2025) · Nature Communications · doi:10.1038/s41467-025-67527-5 · Cited by 8 · see citing works
Patterns of Gastrointestinal Injury Associated With CAR-T Therapy for Patients With Multiple Myeloma.
Osnis, L., Hart, J., Olivas, A., Setia, N., Weber, C., Yassan, L., & Xiao, S. (2025) · American Journal of Surgical Pathology · doi:10.1097/pas.0000000000002499 · Cited by 6
Efficacy and safety of tocilizumab in managing cytokine release syndrome after CD19 CAR-T therapy for relapsed or refractory B-cell acute lymphoblastic leukemia
Zhou, Q., An, Y., Zhang, X., Xiao, X., Bai, X., Liu, P., Pu, Y., Meng, J.-X., Zhu, H.-B., Lyu, C., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1530623 · Cited by 6 · see citing works
“Some studies also suggest that it may cause damage to the blood-brain barrier, allowing in ﬂ ammatory factors and CAR-T cells to enter the central nervous system, thereby potentially increasing the incidence of ICANS (27, 33 – 35).”
Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience
Gavriilaki, E., Mallouri, D., Bousiou, Z., Demosthenous, C., Vardi, A., Dolgyras, P., Batsis, I., Stroggyli, E., Karvouni, P., Masmanidou, M., et al. (2023) · Cancers · doi:10.3390/cancers15174253 · Cited by 6 · see citing works
“CRS is the main risk factor for ICANS since most cases occur after the complete resolution of CRS, suggesting a potential mechanistic link [22,39].”
Background
Systemic Capillary Leak Syndrome (SCLS) Presentation in Patients Receiving Anti-cancer Treatments
Anipindi, M., Kacarow, J., & Bitetto, D. (2023) · Cureus · doi:10.7759/cureus.38335 · Cited by 6 · see citing works
“CAR-T cell therapy used in treating hematological cancers is also associated with SCLS due to severe cytokine release [44-45].”
Background
Sodium oligomannate combined with rivastigmine may improve cerebral blood flow and cognitive impairment following CAR-T cell therapy: A case report
Wang, Y.-L., Zhang, Y., & Xu, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.902301 · Cited by 6 · see citing works
“Although tocilizumab has no effect on most ICANS, it is highly effective in the management of CRS (5, 9).”
BackgroundInfluential
Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities
Chen, L., Chen, F., Niu, H., Li, J., Pu, Y., Yang, C., Wang, Y., Huang, R., Li, K., Lei, Y., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.871661 · Cited by 9 · see citing works
Novel Use of Extracorporeal Blood Purification for Treatment of Severe, Refractory Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy—A Case Report
Singbartl, K., Rosenthal, A., Leis, J., Patel, B. M., & Sen, A. (2021) · Critical Care Explorations · doi:10.1097/cce.0000000000000472 · Cited by 6
“Interleukin (IL)-6, interferon gamma (IFNγ), and granulocyte-macrophage colony-stimulating factor as well as IL-8, IL-10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1b all are considered crucial mediators in this response (2, 3).”
Background
Molecularly targeted therapy and immunotherapy in leukemias
Cousin, É., Picard, A., Oundjian, M., Tardif, N., Quéméner, A. M., Rio, A.-G., Galibert, M., Gandemer, V., & Mazurier, F. (2026) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01775-2 · Cited by 4 · see citing works
“CRS is a systemic inflammatory response that often occurs within 1–4 days after the infusion and can progress to multiple organ failure [389].”
Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes
Armstrong, A., Tang, Y., Mukherjee, N. Z., Zhang, N., & Huang, G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1448201 · Cited by 4 · see citing works
“Similar to septic shock and HLH conditions, cytokine storm has central role in mediating in ﬂ ammation in CRS/ICANS.”
BackgroundInfluential
Construction of CD19 targeted dual- and enhanced dual-antibodies and their efficiency in the treatment of B cell malignancy
Chen, M., Liu, X.-Y., Peng, N., Zhang, T.-M., Mou, J.-L., He, H.-Z., Wang, Y., Xu, Y.-X., Xing, H., Tang, K., et al. (2023) · Experimental Hematology & Oncology · doi:10.1186/s40164-023-00423-0 · Cited by 5 · see citing works
“The efficacies of DuAb and EDuAb in humans have not yet to be evaluated, and the main issue should be addressed is the risk of CRS occurring in bispecific antibodies and CAR-T therapy, which can develop into fatal multiple organ failure in severe cases [32, 33].”
Background
CARing about autoimmune disorders. Use of chimeric antigen receptor engineered T-cells in autoimmune diseases
Tigu, A.-B., Nistor, M., Gulei, D., Constantinescu, C.-S., Kegyes, D., Cenariu, D., Mureșan, X. M., Munteanu, R. A., Feder, R., Jitaru, C., et al. (2025) · Blood Reviews · doi:10.1016/j.blre.2025.101354 · Cited by 3 · see citing works

Authors: Freyer, C. W., & Porter, D. L.
Affiliations: Hospital of the University of Pennsylvania (US)
ORCID: Freyer, Craig W.
Porter, David L.
Venue: Journal of Allergy and Clinical Immunology
Publisher: Elsevier BV
Published: 2020-11
Volume: 146
Issue: 5
Pages: 940-948
ISSN: 0091-6749 (ISSN-L)
DOI: 10.1016/j.jaci.2020.07.025
OpenAlex: W3047493249
Cited by: 216
References: 0
Citations by year: 2026: 40 · 2025: 63 · 2024: 39 · 2023: 37 · 2022: 23 · 2021: 13 · 2020: 1
FWCI: 1.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Allergy and Clinical Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, CAR T-cell therapy, hematologic malignancies, capillary leak syndrome, disseminated intravascular coagulation, hemophagocytic lymphohistiocytosis, tocilizumab, corticosteroids, blood-brain barrier integrity, encephalopathy, cytokine-targeted therapy, immunotherapy toxicity management
MeSH terms: Cytokine Release Syndrome, Interleukin-6 Inhibitors, Adrenal Cortex Hormones, Humans, Interleukin-6, Immunotherapy, Adoptive, Hematologic Neoplasms, Cancer Vaccines, Neurotoxicity Syndromes, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Record

About these checks