Human CD63 has been reported to play a role either as an inhibitor or as a co-stimulator of T- cell responses, although the mechanism of this is unclear. In this study, an anti-human CD63 monoclonal antibody (mAb) COS3A was used to monitor the role of CD63 in T-cell activation. MAb COS3A could inhibit CD3-mediated T-cell proliferation and CD25 expression in peripheral blood mononuclear cells (PBMCs), used as a study model, but the suppressive effect was not observed when purified T-cells were used instead of PBMCs. The inhibitory phenomenon was associated with downregulation of IL-2 and IFN-γ by T-cells, but upregulation of IL-10 by monocytes. Neutralizing IL-10 with anti-IL-10 mAb improved the T-cell response, indicating the role of IL-10 in T-cell suppression. In this study, monocytes were demonstrated to play a role in impeding T-cell activation by the anti-CD63 mAb COS3A. This is the first evidence that anti-CD63 mAb induces IL-10 secretion by monocytes, which later play a role in T-cell hypo-responsiveness.

2019-05-01·Small2区 · 材料科学

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

2区 · 材料科学

Article

作者: Liu, Yuan ; Liu, Chang ; He, Nongyue ; Huang, Rongrong ; He, Lei ; Xu, Hongpan ; Wang, Su ; Xie, Hui ; Li, Zhiyang ; Peng, Lijun ; Liu, Yufeng ; Xia, Yanyan

AbstractEmerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H2O2 and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 102 mL−1 and a linear response range from 4.8 × 103 to 4.8 × 106 exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.

2005-02-07·The Journal of Experimental Medicine1区 · 医学

Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo

1区 · 医学

Article

作者: Lin, Shih-Yao ; Storz, Peter ; Fleming, Tony ; Billingsley, James M. ; Kraft, Stefan ; Jouvin, Marie-Hélène ; Kinet, Jean-Pierre

High-affinity IgE receptor (FcεRI) cross-linking on mast cells (MCs) induces secretion of preformed allergy mediators (degranulation) and synthesis of lipid mediators and cytokines. Degranulation produces many symptoms of immediate-type allergic reactions and is modulated by adhesion to surfaces coated with specific extracellular matrix (ECM) proteins. The signals involved in this modulation are mostly unknown and their contribution to allergic reactions in vivo is unclear. Here we report the generation of monoclonal antibodies that potently suppress FcεRI-induced degranulation, but not leukotriene synthesis. We identified the antibody target as the tetraspanin CD63. Tetraspanins are membrane molecules that form multimolecular complexes with a broad array of molecules including ECM protein-binding β integrins. We found that anti-CD63 inhibits MC adhesion to fibronectin and vitronectin. Furthermore, anti-CD63 inhibits FcεRI-mediated degranulation in cells adherent to those ECM proteins but not in nonadherent cells. Thus the inhibition of degranulation by anti-CD63 correlates with its effect on adhesion. In support of a mechanistic linkage between the two types of inhibition, anti-CD63 had no effect on FcεRI-induced global tyrosine phosphorylation and calcium mobilization but impaired the Gab2–PI3K pathway that is known to be essential for both degranulation and adhesion. Finally, we showed that these antibodies inhibited FcεRI-mediated allergic reactions in vivo. These properties raise the possibility that anti-CD63 could be used as therapeutic agents in MC-dependent diseases.

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适应症	最高研发状态	国家/地区	公司	日期
乳腺癌	药物发现	加拿大	Arius Research, Inc.	-
乳腺癌	药物发现	美国	Genentech, Inc.	-
前列腺癌	药物发现	美国	Genentech, Inc.	-
前列腺癌	药物发现	加拿大	Arius Research, Inc.	-