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Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells.
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State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi, China.
The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.
View Article and Find Full Text PDFImmune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.
View Article and Find Full Text PDFStabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage.
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Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, 24016, USA.
Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature.
View Article and Find Full Text PDFResolution of hypogammaglobulinemia-associated recurrent bacteraemia after hematopoietic cell transplantation (HCT).
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Department of Clinical Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Primary or secondary hypogammaglobulinemia is associated with persistent norovirus and infections despite immunoglobulin replacement therapy. Allogeneic hematopoietic cell transplantation for hematologic indications can lead to immune reconstitution by correcting a previously undiagnosed concurrent primary immunodeficiency.
View Article and Find Full Text PDFMechanisms of HIV-immunologic non-responses and research trends based on gut microbiota.
Front Immunol
January 2025
Department of Preventive Medicine, Medical School of Shihezi University, Shihezi, China.
With the increasing number of people with HIV (PWH) and the use of antiretroviral treatment (ART) for PWH, HIV has gradually become a chronic infectious disease. However, some infected individuals develop issues with immunologic non-responses (INRs) after receiving ART, which can lead to secondary infections and seriously affect the life expectancy and quality of life of PWH. Disruption of the gut microbiota is an important factor in immune activation and inflammation in HIV/AIDS, thus stabilizing the gut microbiota to reduce immune activation and inflammation and promoting immune reconstitution may become a direction for the treatment of HIV/AIDS.
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