AI Article Synopsis
Article Abstract
CD137 (4-1BB) is a costimulatory molecule that can be manipulated for the treatment of cancer and autoimmune disease. Although it is known that agonistic antibodies (mAbs) against CD137 enhance the rejection of murine tumors in a natural killer (NK) cell- and T cell-dependent fashion, the mechanism for NK dependence is poorly understood. In this study, we evaluated the ability of 2 different glycoforms of a chimerized antihuman CD137 mAb, an aglycosylated (GA) and a low fucose form (GG), to react with human NK cells. Both mAbs bound similarly to CD137 and partially blocked the interaction between CD137 and CD137 ligand. However, unlike GA mAb, immobilized GG mAb activated NK cells and enhanced CD137 expression. These effects were seemingly dependent on Fc interaction with putative Fc receptors on the NK-cell surface, as only the immobilized Fc-fragment of GG was required for CD137 expression. Furthermore, CD137 expression could be enhanced with antibodies directed against non-CD137 epitopes, and the expression levels directly correlated with patterns of Fc-glycosylation recognized to improve Fc interaction with Fc gamma receptors. Our data suggest that CD137 can be enhanced on NK cells in an Fc-dependent fashion and that expression correlates with phenotypic and functional parameters of activation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2481534 | PMC |
| http://dx.doi.org/10.1182/blood-2007-11-122465 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Short Communication: Profiling of activated monocyte populations in autism and associations with increased severity and comorbid behaviors.
Brain Behav Immun
December 2024
Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA; MIND Institute, University of California, Sacramento, CA, USA. Electronic address:
Immune dysfunction in autism spectrum disorder (ASD) has been widely reported and is associated with increased impairments in social interactions, communication, repetitive behaviors, anxiety and gastrointestinal problems. Several lines of evidence point towards increased activation of the innate immune system including activation of microglia, increases in innate inflammatory cytokines/chemokines in blood, brain tissue and CSF, activated dendritic cells and macrophages, and abnormal peripheral monocyte cell function. Monocytes are major players in innate immunity and have important functions in the phagocytosis of pathogens or debris, immune defense and cytokine/chemokine production.
View Article and Find Full Text PDFClinical-scale, modular manufacturing of tumor-reactive TILs using a closed and automated culture system.
Front Immunol
December 2024
Research and Development, Miltenyi Biotec, Bergisch Gladbach, Germany.
Recent studies have revealed the potential of tumor-infiltrating lymphocytes (TILs) to treat solid tumors effectively and safely. However, the translation of TIL therapy for patients is still hampered by non-standardized and laborious manufacturing procedures that are expensive and produce highly variable cellular products. To address these limitations, the CliniMACS Prodigy Tumor Reactive T cell (TRT) Process has been developed.
View Article and Find Full Text PDFInduction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137.
Oncoimmunology
December 2025
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers.
View Article and Find Full Text PDFDNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy.
Mol Biol Rep
December 2024
Yunnan Key Laboratory of Laboratory Medicine, Yunnan Province Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
Background: Acute myeloid leukemia (AML) is a common hematological tumor, but it is difficult to treat. DNMT1 is a DNA methyltransferase whose main function is to maintain stable DNA methylation during the DNA replication process. DNMT1 also plays an important role in AML, but its function in cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear.
View Article and Find Full Text PDFThe Efficiency of Brain-Derived Neurotrophic Factor Secretion by mRNA-Electroporated Regulatory T Cells Is Highly Impacted by Their Activation Status.
Eur J Immunol
December 2024
Laboratory of Experimental Hematology, Vaccine and Infections Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Genetic engineering of regulatory T cells (Tregs) presents a promising avenue for advancing immunotherapeutic strategies, particularly in autoimmune diseases and transplantation. This study explores the modification of Tregs via mRNA electroporation, investigating the influence of T-cell activation status on transfection efficiency, phenotype, and functionality. For this CD45RA Tregs were isolated, expanded, and modified to overexpress brain-derived neurotrophic factor (BDNF).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!