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重组CD137-Fc、其合成方法以及在改善免疫系统功能方面的应用,如肿瘤免疫治疗和减轻新型冠状病毒引起的炎症。

Recombinant CD137-Fc, its synthesis, and applications for improving the immune system functions, such as tumor immunotherapy and to reduce the inflammation due to the novel coronavirus.

作者信息

Ajami Maryam, Nazari Mahboobeh, Mahmoodzadeh Habibollah, Moazzeni Seyed Mohammad

机构信息

Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

出版信息

J Cell Biochem. 2021 May 16;122(9):1072-84. doi: 10.1002/jcb.29928.


DOI:10.1002/jcb.29928
PMID:33993519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8242381/
Abstract

CD137 (ILA/4-1BB), a member of tumor necrosis factor receptor superfamily, is one of the most important T cell costimulatory molecules. Interaction of this molecule with its ligand transmits a two-way signal that activates both T lymphocyte and antigen presenting cells. The soluble form of CD137 (sCD137) reduces the activity of its membrane isoform and is associated with T lymphocyte activation-induced cell death. Recombinant CD137-Fc may be used to treat cancers, autoimmune disorders and viral infections. It may also be useful for management of coronavirus infection. The 1276 bp DNA sequence encoded CD137-Fc recombinant protein was prepared and subcloned into lentiviral vector and expressed in transduced CHO-K1 eukaryotic cells. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, and enzyme-linked immunosorbent assay analysis results demonstrated that the expression of the 70-kDa CD137-Fc molecule was detectable without any degradation. This study helps to confirm previous research suggesting the use of this recombinant protein as a promising solution for the treatment of virus infections. CD137-Fc fusion protein could also make immunotherapy more effective for some diseases. This product is widely used in novel medical treatments, including cell-based immunotherapy such as dendritic cell, CAR T and CAR NK therapy. Its production and usage in research and treatment is noticeable also in current coronavirus disease 2019 pandemic.

摘要

CD137(ILA/4-1BB)是肿瘤坏死因子受体超家族的一员,是最重要的T细胞共刺激分子之一。该分子与其配体的相互作用传递双向信号,激活T淋巴细胞和抗原呈递细胞。可溶性形式的CD137(sCD137)会降低其膜异构体的活性,并与T淋巴细胞活化诱导的细胞死亡相关。重组CD137-Fc可用于治疗癌症、自身免疫性疾病和病毒感染。它可能对冠状病毒感染的管理也有用。制备了编码CD137-Fc重组蛋白的1276 bp DNA序列,并将其亚克隆到慢病毒载体中,在转导的CHO-K1真核细胞中表达。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、蛋白质免疫印迹分析和酶联免疫吸附测定分析结果表明,可检测到70 kDa的CD137-Fc分子表达,且无任何降解。本研究有助于证实先前的研究,即该重组蛋白有望用于治疗病毒感染。CD137-Fc融合蛋白还可使某些疾病的免疫治疗更有效。该产品广泛应用于新型医学治疗,包括基于细胞的免疫治疗,如树突状细胞、嵌合抗原受体T细胞和嵌合抗原受体自然杀伤细胞疗法。在当前的2019冠状病毒病大流行中,其在研究和治疗中的生产及应用也值得关注。

相似文献

[1]
Recombinant CD137-Fc, its synthesis, and applications for improving the immune system functions, such as tumor immunotherapy and to reduce the inflammation due to the novel coronavirus.

J Cell Biochem. 2021-5-16

[2]
Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies.

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[3]
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[4]
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Eur J Immunol. 1998-1

[5]
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[6]
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Iran J Immunol. 2023-3-14

[7]
The relevance of soluble CD137 in the regulation of immune responses and for immunotherapeutic intervention.

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[8]
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Front Immunol. 2022

[9]
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[10]
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引用本文的文献

[1]
Soluble CD137 as a potential biomarker for severe COVID-19.

Immunol Lett. 2022-7-8

本文引用的文献

[1]
The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system.

Cytokine Growth Factor Rev. 2020-5-11

[2]
The relevance of soluble CD137 in the regulation of immune responses and for immunotherapeutic intervention.

J Leukoc Biol. 2020-2-13

[3]
Soluble CD137 Ameliorates Acute Type 1 Diabetes by Inducing T Cell Anergy.

Front Immunol. 2019-11-7

[4]
CD137L-DCs, Potent Immune-Stimulators-History, Characteristics, and Perspectives.

Front Immunol. 2019-10-2

[5]
CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis.

Blood. 2019-10-31

[6]
The Progress of Investigating the CD137-CD137L Axis as a Potential Target for Systemic Lupus Erythematosus.

Cells. 2019-9-6

[7]
An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer.

Int J Mol Sci. 2019-4-12

[8]
Reverse Signaling of Tumor Necrosis Factor Superfamily Proteins in Macrophages and Microglia: Superfamily Portrait in the Neuroimmune Interface.

Front Immunol. 2019-2-19

[9]
The use of immunotherapy in the treatment of melanoma.

J Hematol Oncol. 2017-4-24

[10]
Human CD4(+) T-Cells: A Role for Low-Affinity Fc Receptors.

Front Immunol. 2016-6-1

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