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Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer strain that delivers GM-CSF.
Acta Pharm Sin B
December 2024
Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea.
Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor.
View Article and Find Full Text PDFLipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity.
Mol Cancer
January 2025
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.
View Article and Find Full Text PDFA humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.
J Transl Med
January 2025
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.
Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.
Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.
Precision Prediction of Alzheimer's Disease: Integrating Mitochondrial Energy Metabolism and Immunological Insights.
J Mol Neurosci
January 2025
Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Alzheimer's disease (AD), a prevalent neurodegenerative disorder, is characterized by mitochondrial dysfunction and immune dysregulation. This study is aimed at developing a risk prediction model for AD by integrating multi-omics data and exploring the interplay between mitochondrial energy metabolism-related genes (MEMRGs) and immune cell dynamics. We integrated four GEO datasets (GSE132903, GSE29378, GSE33000, GSE5281) for differential gene expression analysis, functional enrichment, and weighted gene co-expression network analysis (WGCNA).
View Article and Find Full Text PDFETV7 limits the antiviral and antitumor efficacy of CD8 T cells by diverting their fate toward exhaustion.
Nat Cancer
January 2025
State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
Terminal exhaustion is a critical barrier to antitumor immunity. By integrating and analyzing single-cell RNA-sequencing and single-cell assay for transposase-accessible chromatin with sequencing data, we found that ETS variant 7 (ETV7) is indispensable for determining CD8 T cell fate in tumors. ETV7 introduction drives T cell differentiation from memory to terminal exhaustion, limiting antiviral and antitumor efficacy in male mice.
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