CAR-T cell therapies have risen to prominence over the last decade, and their indications are increasing with several products approved as early as second line in Large B Cell non-Hodgkin Lymphomas. Their major toxicities are the cytokine release syndrome (CRS) and the Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS). These entities involve a hyperinflammatory cascade which is amplified through the mononuclear phagocytic system (MPS). Herein, we review the immune mediated adverse events related to CAR therapy, including their pathophysiologies, and current therapies. In particular, we discuss the emerging role of the MPS in both the toxicity and efficacy of CAR-T therapy, and possible avenues for the modulation of the MPS to optimize efficacy while minimizing toxicity.
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http://dx.doi.org/10.1007/s12672-025-01776-0 | DOI Listing |
Front Immunol
January 2025
Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
Background: Chimeric antigen receptor T (CAR-T) cell therapy is more effective in relapsed or refractory diffuse large B cell lymphoma (DLBCL) than other therapies, but a high proportion of patients relapse after CAR-T cell therapy owing to antigen escape, limited persistence of CAR-T cells, and immunosuppression in the tumor microenvironment. CAR-T cell exhaustion is a major cause of relapse. Epigenetic modifications can regulate T cell activation, maturation and depletion; they can be applied to reduce T cell depletion, improve infiltration, and promote memory phenotype formation to reduce relapse after CAR-T cell therapy.
View Article and Find Full Text PDFCancer Rep (Hoboken)
January 2025
Department of Adult Lymphoma, Beijing Boren Hospital, Beijing, China.
Objective: Currently, chimeric antigen receptor T-cell (CART) therapy represents a highly effective approach for relapsed/refractory B-cell lymphomas. However, it also carries treatment-related risks. Limited data are available on the risks associated with CART therapy in patients with gastrointestinal involvement in B-cell lymphomas.
View Article and Find Full Text PDFSmall Methods
January 2025
Division of Thoracic Tumor Multimodality Treatment, Department of Radiation Oncology, Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, Cancer Center, Breast Center, Institute of Breast Health Medicine, Laboratory of Clinical Cell Therapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Non-small cell lung cancer (NSCLC) has a strikingly high incidence rate globally. Although immunotherapy brings a great breakthrough in its clinical treatment of NSCLC, significant challenges still need to be overcome. The development of novel multi-functional nanomedicines in the realm of tumor immunotherapy offers promising opportunities for NSCLC patients, as nanomedicines exhibit significant advantages, including specific targeting of tumor cells, improved drug bioavailability, reduced systemic toxicity, and overcoming of immune resistance.
View Article and Find Full Text PDFSci Rep
January 2025
The Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.
Cell-penetrating peptides (CPPs) have been shown to have superior material transport ability because poor infiltration of activated lymphocytes into tumors is one of the crucial factors limiting the therapeutic effect of tumor immunotherapy. Numerous studies have investigated the potential application of CPPs in tumor immunotherapy. This review delves into the crucial role that CPPs play in enhancing tumor immunotherapy, emphasizing their impact on various immunotherapy strategies, such as cytokine therapy, adoptive cell therapy, cancer vaccines, and immune checkpoint inhibitors.
View Article and Find Full Text PDFACS Nano
January 2025
Department of Bioengineering, University of Washington, Seattle, Washington 98195-5061, United States.
The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.
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