With immunotherapy innovations for cancer treatment, in particular chimeric antigen receptor (CAR) T cells, becoming more successful and prevalent, strategies to mitigate and manage their toxicities are required. Anti-CD19 CAR T-cell therapy has revolutionized the treatment of relapsed/refractory pediatric and adult acute lymphoblastic leukemia and refractory adult non-Hodgkin lymphoma, resulting in the expanded use of CAR T cells in multicenter trials and as US FDA-approved products. Cytokine release syndrome (CRS) and CAR-associated neurotoxicity, which can occur independently or concurrently with CRS, are two potentially life-threatening toxicities of CAR T-cell therapy. In this review, we will focus on describing the pathophysiology behind CRS, the proposed definitions of and grading systems for CRS, and innovative options for treating this potentially lethal systemic inflammatory condition.
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http://dx.doi.org/10.2147/TCRM.S150524 | DOI Listing |
Target Oncol
January 2025
Berenson Cancer Center, West Hollywood, CA, USA.
Multiple myeloma (MM) is a bone-marrow-based cancer of plasma cells. Over the last 2 decades, marked treatment advances have led to improvements in the overall survival (OS) of patients with this disease. Key developments include the use of chemotherapy, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies.
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Kinimmune, Inc. St. Louis, 63141, Missouri, USA.
PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.
View Article and Find Full Text PDFStem Cells
January 2025
Sangamo Therapeutics, 501 Canal Blvd. Richmond, CA.
iPSCs can serve as a renewable source of a consistent edited cell product, overcoming limitations of primary cells. While feeder-free generation of clinical grade iPSC-derived CD8 T cells has been achieved, differentiation of iPSC-derived CD4sp and regulatory T cells requires mouse stromal cells in an artificial thymic organoid. Here we report a serum- and feeder-free differentiation process suitable for large-scale production.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Department of Research, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
Background: Stroke remains a leading cause of mortality and disability among adults. Given the restricted therapeutic window for intravascular interventions and neuroprotection during the acute phase, there has been a growing focus on tissue repair and functional recovery in the subacute and chronic phases after stroke. The pro-inflammatory microglial polarization occurs in subacute and chronic phases after stroke and may represent therapeutic targets for stroke recovery.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Science and Technology of China School of Biomedical Engineering, Department of Polymer Science and Engineering, 96 Jinzhai Road, 230026, Hefei, CHINA.
Lipid nanoparticles (LNPs) based messenger RNA (mRNA) therapeutics hold immense promise for treating a wide array of diseases, while their nonhepatic organs targeting and insufficient endosomal escape efficiency remain challenges. For LNPs, polyethylene glycol (PEG) lipids have a crucial role in stabilizing them in aqueous medium, but they severely hinder cellular uptake and reduce transfection efficiency. In this study, we designed ultrasound (US)-assisted fluorinated PEGylated LNPs (F-LNPs) to enhance spleen-targeted mRNA delivery and transfection.
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