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Chemokine-immunoglobulin fusion polypeptides, compositions, method of making and use thereof

An immunoglobulin and fusion polypeptide technology, which is applied in the fields of chemokine-immunoglobulin fusion polypeptides, compositions and their preparation and use, and can solve the problems of chronic unhealed wounds, reduction and the like

Inactive Publication Date: 2014-06-11
JYANT TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Impaired wound healing in diabetic patients is accompanied by reduced early inflammatory cell infiltration but persistence of neutrophils and macrophages contributes to chronic non-healing wounds

Method used

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  • Chemokine-immunoglobulin fusion polypeptides, compositions, method of making and use thereof
  • Chemokine-immunoglobulin fusion polypeptides, compositions, method of making and use thereof
  • Chemokine-immunoglobulin fusion polypeptides, compositions, method of making and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0180] Embodiment 1: Generation of plasmid expression vector

[0181] pFUSE-hIgG1-Fc1, pFUSE-hIgG2-Fc1, pFUSE-hIgG3-Fc1, and pFUSE-hIgG4-Fc1 vectors from InvivoGen (San Diego, CA) were used to generate chemokine-hIgG4-Fc1-expressing immunoglobulins using standard molecular biology methods. Expression vector of protein fusion polypeptide. Examples of such expression vectors are shown in Figures 1-10.

Embodiment 2

[0182] Example 2: Expression of Chemokine Receptors in Breast Cancer Cell Lines

[0183] Experiments were performed to compare the expression levels of CXCR7 and CXCR3 in breast cancer tissues at different stages, in non-neoplastic breast tissues. Non-neoplastic breast tissue did not express detectable levels of CXCR7. CXCR7 expression was significantly higher in advanced breast cancer tissues compared with non-neoplastic breast tissues. Both CXCR7 and CXCR3 mRNA were elevated in breast cancer cell line (MDA-MB-231 ) compared to normal breast cells (MCF-10A).

Embodiment 3

[0184] Example 3: var-CXCL11-IgG fusion polypeptide inhibits the activation of CXCR7 and CXCR3 in breast cancer cells

[0185] Using Amnis ImageStream analysis, the inventors found that CXCL11 stimulates the aggregation and rapid desensitization of CXCR3 and CXCR7, ie CXCL12 regulates modest CXCR7 clustering, and adrenomedullin (AM) stimulates CXCR3 and CXCR7 clustering. CXCL11-IgG fusion polypeptide abolishes CXCR3 and CXCR7, but not CXCR4, clustering and desensitization by CXCL11, CXCL12 and AM.

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Abstract

This application is directed to chemokine-immunoglobulin fusion polypeptides and chemokine-polymer conjugates. The fusion polypeptides and conjugates can be used for treating chemokine receptor-mediated disorders and modulating inflammation, inflammatory cell motility, cancer cell motility, or cancer cell survival.

Description

[0001] This application claims priority to US Provisional Patent Application 61 / 492,260, filed June 1, 2011. The entire content of the aforementioned application is hereby incorporated by reference. technical field [0002] The present application relates generally to compositions that can be used to treat chemokine receptor mediated disorders and to modulate inflammation, inflammatory cell motility, cancer cell motility, or cancer cell survival. Background technique [0003] Chemokines are chemotactic cytokines, with a molecular weight of 6 kDa to 15 kDa, released by many various cells to attract and activate macrophages, T and B lymphocytes, eosinophils, basophils, and neutrophils granulocytes and other cell types. There are 4 types of chemokines, namely CXC, CC, C and CX3C, according to whether the first two cysteines in the amino acid sequence are separated by a single amino acid (CXC) or are contiguous (CC). Unlike other chemokines, C chemokine has only two cysteines;...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61K38/17A61K48/00A61P35/00
CPCC07K14/521A61K38/00C07K16/2866C07K2319/30A61P1/00A61P11/00A61P13/00A61P15/00A61P17/00A61P19/00A61P21/00A61P25/00A61P27/02A61P29/00A61P31/00A61P31/04A61P35/00A61P35/02A61P37/02A61P9/00Y02A50/30
Inventor 詹姆斯·W·利拉德
Owner JYANT TECH
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