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Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.
Nat Med
January 2025
Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.
View Article and Find Full Text PDFCD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.
iScience
January 2025
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.
View Article and Find Full Text PDFIn situ production and precise release of bioactive GM-CSF and siRNA by engineered bacteria for macrophage reprogramming in cancer immunotherapy.
Biomaterials
December 2024
School of Life Sciences, Faculty of Medicine, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin University, Tianjin, 300072, China.
In the immunosuppressive tumor microenvironment (TME), tumor-associated macrophages (TAMs) predominantly exhibit an immunosuppressive M2 phenotype, which facilitates tumor proliferation and metastasis. Although current strategies aimed at reprogramming TAMs hold promise, their sustainability and effectiveness are limited due to repeated injections. Herein, a bacterial therapy platform containing two engineered strains was developed.
View Article and Find Full Text PDFMetabolic Stress expands Polyfunctional, Proinflammatory Th cells in Psoriatic Arthritis, where there is IL-23-independent IL-17 production.
Arthritis Rheumatol
December 2024
Department of Medicine, University of Cambridge, Cambridge University Hospitals NHS FT, Cambridge, U.K.
Objective: Genetic associations and blockade of the interleukin-23/IL-17 axis with monoclonal antibodies support a role for this pathway in psoriatic arthritis (PsA). This study examines the requirement of IL-23 for IL-17 production, and the role of the metabolic microenvironment in the expansion of Th-derived cells in PsA.
Methods: PsA patient synovial fluid or peripheral blood Th cell frequencies were evaluated by flow cytometry using CCR6, CD161 and T-bet as phenotypic markers, and the cytokines IFN-γ, GM-CSF and IL-17 assessed by flow cytometry and ELISA.
Adverse Reaction Reporting for Naxitamab in Chinese Expanded Access Treatment for Relapsed/Refractory High-Risk Neuroblastoma at the Children's Hospital of Fudan University.
Drugs Real World Outcomes
December 2024
Children's Hospital of Fudan University, 399 Wanyuan Road, Minhang District, Shanghai, China.
Background: The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children's Hospital of Fudan University, Shanghai, China, in August 2021.
Objective: We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022.
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