Chimeric Antigen Receptor (CAR) T-cell therapies represents a major advancement in the treatment of refractory hematologic malignancies, with high remission rates for relapsed B-cell lymphomas and leukemias. However, it is associated with a broad spectrum of potentially life-threatening toxicities, many of which require intensive care unit (ICU) management. Key complications include Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), as well as severe infections, Immune Effector Cell-associated Hematotoxicity (ICAHT), coagulopathies, and organ dysfunctions resulting from the intense inflammatory response induced by CAR T-cells. Approximately one third of patients undergoing CAR T-cell therapy require ICU admission. Among those patients, CRS is the leading indication. ICANS and sepsis are other major causes of admission to the ICU. This review provides a comprehensive overview of ICU considerations for managing CAR T-cell-related toxicities, covering criteria for ICU admission, approaches to grading and treating complications, and interdisciplinary recommendations to optimize patient outcomes. Enhanced awareness and early intervention are critical in reducing ICU mortality and improving overall survival in patients receiving CAR T-cell therapy.
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http://dx.doi.org/10.1016/j.rmed.2025.107958 | DOI Listing |
Mol Ther
January 2025
Brown Center for Immunotherapy. Indiana University School of Medicine. 975 W. Walnut St., IB554A, Indianapolis, IN 46202. Electronic address:
Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized cancer treatment and is now being explored for other diseases, such as autoimmune disorders. While the tumor microenvironment (TME) in cancer is often immunosuppressive, in autoimmune diseases, the environment is typically inflammatory. Both environments can negatively impact CAR T cell survival: the former through direct suppression, hypoxia, and nutrient deprivation, and the latter through chronic T cell receptor (TCR) engagement, risking exhaustion.
View Article and Find Full Text PDFMol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFBone Marrow Transplant
January 2025
Université de Franche-Comté, EFS, INSERM, UMR RIGHT, F-, 25000, Besançon, France.
The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Cellular Immunotherapy Research Unit, Chulalongkorn University, Bangkok, Thailand
Background: B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.
Methods: Expression of B7-H3 across various solid tumors was evaluated using RNA-seq data from TCGA, TARGET, and GTEx datasets and by flow cytometry staining.
Int Immunopharmacol
January 2025
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan Province, People's Republic of China. Electronic address:
Chimeric antigen receptor T (CAR-T) cell therapy targeting B cell mature antigen (BCMA) has shown remarkable clinical benefits in treating multiple myeloma (MM). Bortezomib, a proteasome inhibitor approved as a first-line agent for MM for two decades, has demonstrated potent antitumor activity. In this study, we found that bortezomib treatment stabilizes the expression of BCMA and conceived the hypothesis that BCMA CAR-T therapy combined with bortezomib would enhance the anti-MM efficacy.
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