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

A technology of immunoglobulin and chemokines, applied in the composition of cancer cell motility or cancer cell survival, regulating inflammation, inflammatory cell motility, and can solve non-healing wounds, chronic problems, etc.

Inactive Publication Date: 2017-09-26
JYANT TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Impaired wound healing in diabetic patients is accompanied by reduced early inflammatory cell infiltration, but persistence of neutrophils and macrophages leads to chronic, nonhealing 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

[0183] Example 1: Production of plasmid expression vectors

[0184] pFUSE-hIgG1-Fc1, pFUSE-hIgG2-Fc1, pFUSE-hIgG3-Fc1, and pFUSE-hIgG4-Fc1 vectors from InvivoGen (San Diego, CA) were generated using standard molecular biology methods capable of expressing chemokine-immunoglobulin fusions. Polypeptide expression vector. Examples of such expression vectors are shown in Figures 1-10.

Embodiment 2

[0185] Example 2: Expression of Chemokine Receptors in Breast Cancer Cell Lines

[0186] In non-neoplastic breast tissues, experiments were performed in various stages of breast cancer tissues to compare the expression levels of CXCR7 and CXCR3. 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. CXCR7 and CXCR3 mRNA were also elevated in breast cancer cell line (MDA-MB-231 ) compared to normal breast cells (MCF-10A).

Embodiment 3

[0187] Example 3: var-CXCL11-IgG fusion polypeptide inhibits CXCR7 and CXCR3 activation in breast cancer cells

[0188] Using Amnis ImageStream analysis, we found that CXCL11 stimulates the aggregation and rapid desensitization of CXCR3 and CXCR7, CXCL12 regulates modest CXCR7 clustering, and adrenomedullin (AM) stimulates CXCR3 and CXCR7 clustering. CXCL11-IgG fusion polypeptides abolish CXCR3 and CXCR7, but not CXCR4, cluster and desensitize 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 Patent Application Serial No. 14 / 612,884, filed February 3, 2015. The entire content of the above application is incorporated herein by reference. technical field [0002] The present application relates generally to compositions that can be used in the treatment of chemokine receptor mediated diseases and in the modulation of inflammation, inflammatory cell motility, cancer cell motility or cancer cell survival. Background technique [0003] Chemokines are chemotactic cytokines with a molecular weight of 6-15 kDa that are released by various cells to attract and activate macrophages, T and B lymphocytes, eosinophils, basophils among other cell types and neutrophils. There are four classes of chemokines, CXC, CC, C and CX3C, depending on whether the first two cysteines in the amino acid sequence are separated by a single amino acid (CXC) or adjacent (CC). Unlike other chemokines, C chemokines have only two cysteines; one N-term...

Claims

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Application Information

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IPC IPC(8): C07K16/28A61K39/395
CPCC07K14/521C07K2319/30
Inventor 詹姆斯·W·利拉德
Owner JYANT TECH