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Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.
Neurol Neuroimmunol Neuroinflamm
March 2025
Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney.
Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.
View Article and Find Full Text PDFCD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).
View Article and Find Full Text PDFRole of procalcitonin, C reactive protein and ferritin in cytokine release syndrome after CAR T-cell therapy in children and young adults.
Biomarkers
January 2025
Pediatric Intensive Care Unit, Hospital Sant Joan de Déu-University of Barcelona, Barcelona, Spain.
PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity.
View Article and Find Full Text PDFTranscriptomics-based analysis of neurotoxic and reproductive effects in turbot (Scophthalmus maximus) after exposure to tris (2-chloroethyl) phosphate (TCEP).
BMC Genomics
January 2025
Laboratory for Marine Ecology and Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, 266061, China.
Background: Tris (2-chloroethyl) phosphate (TCEP), a widely used flame retardant, is widespread in the environment and potentially harmful to organisms. However, the specific mechanisms of TCEP-induced neurological and reproductive toxicity in fish are largely unknown. Turbot (Scophthalmus maximus) is cultivated on a large scale, and the emergence of pollutants with endocrine disrupting effects seriously affects its economic benefits.
View Article and Find Full Text PDFDonor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma.
Nat Med
January 2025
Department of Hematology/Oncology, Cell and Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Bambino Gesù Children's Hospital, Rome, Italy.
Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation.
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