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Genetic Disruption of Blimp-1 Drastically Augments the Antitumor Efficacy of BCMA-Targeting CAR-T Cells.
Blood Adv
December 2024
Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Chimeric antigen receptor-T (CAR-T) cells directed against B-cell maturation antigen (BCMA) are an effective treatment for multiple myeloma (MM), but short persistence and frequent relapses are challenges for this immunotherapy. This lack of durability has been attributed to the premature terminal differentiation of CAR-T cells which prevents the formation of long-lived memory cells that maintain anti-tumour responses. To improve long-term efficacy, we used CRISPR/Cas9-mediated gene editing to ablate the expression of the transcription factor Blimp-1.
View Article and Find Full Text PDFAntitumour vaccination via the targeted proteolysis of antigens isolated from tumour lysates.
Nat Biomed Eng
November 2024
Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
The activation of cytotoxic T cells against tumour cells typically requires the cross-presentation, by antigen-presenting cells (and via major histocompatibility complex class I molecules), of an epitope derived from a tumour antigen. A critical step in antigen processing is the proteolysis of tumour antigens mediated by the ubiquitin-proteasome pathway. Here we describe a tumour vaccine leveraging targeted antigen degradation to augment antigen processing and cross-presentation.
View Article and Find Full Text PDFTargeting METTL3 as a checkpoint to enhance T cells for tumour immunotherapy.
Clin Transl Med
November 2024
Center for Cell Lineage and Development, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Background: Immunotherapy has emerged as a crucial treatment modality for solid tumours, yet tumours often evade immune surveillance. There is an imperative to uncover novel immune regulators that can boost tumour immunogenicity and increase the efficacy of immune checkpoint blockade (ICB) therapy. Epigenetic regulators play critical roles in tumour microenvironment remodelling, and N6-methyladenosine (mA) is known to be involved in tumourigenesis.
View Article and Find Full Text PDFReactive oxygen species augmented polydopamine-chlorin e6 nanosystem for enhanced chemo/photothermal/photodynamic therapy: A synergistic trimodal combination approach in vitro & in vivo.
Int J Biol Macromol
December 2024
Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Chiba, Japan.
Article Synopsis
- The study explores a new cancer treatment approach that combines near-infrared laser phototherapies with chemotherapy, aiming to improve effectiveness while minimizing invasiveness and side effects.
- CuO nanoparticles were modified with a photosensitizer, chlorin e6, and coated with polydopamine to create a multifunctional drug delivery system that enhances targeted therapy.
- In vitro and in vivo experiments demonstrated that this nanoplatform, when used with laser irradiation, effectively increases cancer cell death and shows promise as a combined treatment strategy for better cancer management.
Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma.
Gut
November 2024
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
Background: Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood.
Objective: We aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC).
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