A novel fusion protein of IP10-scFv retains antibody specificity and chemokine function

Guo, Junqing; Chen, Liu; Ai, Hongwu; Jing, Jian-Nian; Zhou, Jiyong; Zhang, Chuyu; Shangyou, You

doi:10.1016/j.bbrc.2004.05.193

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…In addition, previous studies (17,18) also reported that CXCR3 was predominately expressed and upregulated significantly in HCC cancer tissues compared with adjacent non-cancerous tissues. Meanwhile, the expression of CXCR3 was significantly increased in certain hepatic cell lines, including HepG2 (19), Huh-7 (20) and SMMC-7721 (21). Therefore, it was confirmed that CXCR3 was highly expressed in HCC cell lines and HCC human samples (17,18).…”

Section: Discussionmentioning

confidence: 81%

COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species

You

Huang

et al. 2018

Mol Med Report

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While >80% of the incidence occurs in sub‑Saharan Africa and East Asia, cases of hepatocellular carcinoma (HCC) have been rapidly increasing in Western countries. Despite its global importance, HCC is relatively under‑researched compared with other lethal cancer types, which is possibly due to the high complexity and heterogeneity of HCC. It has been reported previously that COMM domain‑containing protein 7 (COMMD7) is upregulated in HCC and promotes HCC cell proliferation by triggering C‑X‑C motif chemokine 10 (CXCL10) production. However, the value of targeting CXCL10 signal transduction in treating COMMD7‑positive tumors, or the molecular mechanisms underlying COMMD7‑mediated CXCL10 expression, has not been completely addressed. In the present study, it was demonstrated that disruption of the CXCL10/C‑X‑C chemokine receptor type 3 axis reduces COMMD7‑mediated HCC cell proliferation. Furthermore, COMMD7 modulates CXCL10 production by activating nuclear factor (NF)‑κB. Additionally, it was demonstrated that intracellular reactive oxygen species (ROS) are required for NF‑κB activation and CXCL10 production. In conclusion, COMMD7 activates CXCL10 production by regulating NF‑κB and the production of ROS. The present study highlighted the role of COMMD7 in the development of HCC, and provides novel options for anticancer drug design.

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Section: Discussionmentioning

confidence: 81%

COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species

You

Huang

et al. 2018

Mol Med Report

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“…Cell migration was examined using a 48-well microchemotaxis assay as described previously [5,6] . Cell migration was examined using a 48-well microchemotaxis assay as described previously [5,6] .…”

Section: Chemotaxis Assaysmentioning

confidence: 99%

Construction of eukaryotic expression vector for human CCL21 and characterization of its chemotactic activity

Hou

Liu

Jiao

et al. 2006

Chin. J. Cancer Res.

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Objective:To obtain recombinant human CCL21 with biological activity from eukaryotic expression system for further use in cancer gene therapy. Methods: A fragment of human CCL21 gene was obtained from pSK-hCCL21 plasmid digested by Xho I and BamH I, inserted into the responding sites of eukaryotic expression vector pVAX1, and then transfected into COS-7 cells by electroporation method. The expression of hCCL21 protein was detected by western blotting analysis. The in vitro chemotaxis assay was used to test the chemotactic function of the expression product to lymphocytes. Results: Human CCL21 protein was expressed by transfected COS-7 cells with recombinant plasmid containing hCCL21 gene, and was verified by western blotting. The in vitro chemotaxis assay demonstrated that human CCL21 protein had a potent chemotactic function to lymphocytes. Conclusion: Human CCL21 was successfully and transiently expressed in eukaryotic cells, which lays some foundation for the study of CCL21 gene therapy in murine tumor models.

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“…To the best of our knowledge, only few reports on antibody-chemokine fusion proteins ('immunochemokines') have been published so far. [8][9][10] Chemokines are a family of structurally related chemotactic cytokines of small molecular weight that are acting in gradients to promote directional migration of leukocytes, epithelial, and endothelial cells. 11 Some chemokines can have additional activities including HIV inhibitory activity, tumor-promoting or -inhibitory activity, angiogenic or angiostatic activity or the ability to modulate gene expression, phagocyte activation, and cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…In a third report, featuring the use of a recombinant murine antibody fragment specific to human acidic isoferritin in single-chain Fv (scFv) format, the fusion protein mCXCL10-scFv could be expressed 8,46 and the immunochemokine retained its antibody-binding specificity and chemokine function, but was not tested in vivo for biological activity and for therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of antibody–chemokine fusion proteins for tumor-targeting applications

Hess

Neri

2014

Exp Biol Med (Maywood)

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There is an increasing biotechnological interest in the 'arming' of therapeutic antibodies with bioactive payloads. While many antibody-cytokine fusion proteins have been extensively investigated in preclinical and clinical studies, there are only few reports related to antibody-chemokine fusion proteins ('immunochemokines'). Here, we describe the cloning, expression, and characterization of 10 immunochemokines based on the monoclonal antibody F8, specific to the alternatively spliced extra domain A (EDA) of fibronectin, a marker of angiogenesis. Among the 10 murine chemokines tested in our study, only CCL19, CCL20, CCL21, and CXCL10 could be expressed and isolated at acceptable purity levels as F8-based fusion proteins. The immunochemokines retained the binding characteristics of the parental antibody, but could not be characterized by gel-filtration analysis, an analytical limitation which had previously been observed in our laboratory for the unconjugated chemokines. When radioiodinated preparations of CCL19-F8, CCL20-F8, CCL21-F8, and CXCL10-F8 were tested in quantitative biodistribution studies in tumor-bearing mice, the four fusion proteins failed to preferentially accumulate at the tumor site, while the unconjugated parental antibody displayed a tumor:blood ratio >20:1, 24 h after intravenous (i.v.) administration. The tumor-targeting ability of CCL19-F8 could be rescued only in part by preadministration of unlabeled CCL19-F8, indicating that a chemokine trapping mechanism may hinder pharmacodelivery strategies. While this article highlights expression, analytical, and biodistribution challenges associated with the antibody-based in vivo delivery of chemokines at sites of disease, it provides the first comprehensive report in this field and may facilitate future studies with immunochemokines.

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A novel fusion protein of IP10-scFv retains antibody specificity and chemokine function

Cited by 10 publications

References 32 publications

COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species

COMMD7 activates CXCL10 production by regulating NF-κB and the production of reactive oxygen species

Construction of eukaryotic expression vector for human CCL21 and characterization of its chemotactic activity

Evaluation of antibody–chemokine fusion proteins for tumor-targeting applications

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