Eotaxin-2 (CCL24) inhibitors in inflammatory, autoimmune and cardiovascular disorders

An autoimmune disease, eosinophilic technology, applied in cardiovascular system diseases, cytokines/lymphokines/interferons, anti-inflammatory agents, etc.

Inactive Publication Date: 2012-01-04
特拉维夫医学中心医学研究,基础设施及健康服务基金
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The eotaxin-3 gene is close to the eotaxin-2 gene on chromosome 7, but shares only 33% homology with it

Method used

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  • Eotaxin-2 (CCL24) inhibitors in inflammatory, autoimmune and cardiovascular disorders
  • Eotaxin-2 (CCL24) inhibitors in inflammatory, autoimmune and cardiovascular disorders
  • Eotaxin-2 (CCL24) inhibitors in inflammatory, autoimmune and cardiovascular disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0152] Example 1: Specificity and anti-inflammatory effects of anti-eotaxin-2 mAb (D8)

[0153] Multiple anti-eotaxin-2 murine monoclonal antibodies (mAbs) were prepared as described above.

[0154] The nucleic acid sequence encoding of the heavy chain of the D8 antibody is as follows:

[0155] SEQ ID NO: 1:

[0156] GGGCAGCAGANCCGGGGCNGNGGATAGACAGANGGGGGNNGNCGTTTTGGCTGA

[0157] GGAGACGGTGACTGAGGTTCCTTGACCCCAGTTGTCCATAGCGTAGCTACTACCGTAGGA

[0158] ATGACTTGCACAGAAATATG

[0159] TAGCCGTGTCCTCATTTCTGAGGTTGTTGATCTGCAAATAGGCAGTGCTGGCAGAGGTTTC

[0160] CAAAGAGAGGGCAAACCGT

[0161] CCCTTGAAGTCATCAGTATATGTTGGCTCTCCATTGTAGGTGTTGATCCAGCCCATCCACTT

[0162] TAAACCCTTTCCTGGAGC

[0163] CTGCTTTACCCAGTTCATTCCAGAGTTTGTGAAGGGATACCCAGAAGCCCTGCAGGAGATC

[0164] TTGACTGTGTCTCCAGGCT

[0165] T℃TTCAGCTCANGTCCAGACTGCACCAACTGGATCTGGGCCATGGCCNGCTA

[0166] The nucleic acid sequence coding of D8 antibody light chain (kappa) is as follows:

[0167] SEQ ID NO: 2:

[0168] GGGCCAATGGNNGAGGACG...

Embodiment 2

[0222] Example 2: Anti-inflammatory potential of cloned D8 mAb (in vivo data)

[0223] A. Rheumatoid Arthritis Model

[0224] Adjuvant arthritis was induced in Lewis mice (6-week-old Lewis mice obtained from Harlan, Israel) by injection of incomplete Freund's adjuvant. Incomplete Freund's adjuvant was used to inactivate Mycobacterium tuberculosis (Difco, Detroit, MI) by heat in mineral oil at a concentration of 10 mg / ml. 100 μl of adjuvant was injected subcutaneously into the tail of mice. Arthritis developed 10 days after injection.

[0225] Assessment of the effect of antagonism - eotaxin-2 antibody, adjuvant-induced arthritis compared to non-specific IgG and PBS as controls:

[0226] Mice (8 in each group) were injected intraperitoneally (IP) with 3 monoclonal antibodies against eotaxin-2, (D8, G8, G7) 3X / week. All mice in the control group (non-specific) were treated with IgG or PBS. Injections were performed on the third day after adjuvant administration, three times...

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Abstract

The present invention is based on the finding that inhibition of eotaxin-2 by polyclonal or monoclonal antibodies, has a significant protective effect in animal models of inflammatory diseases such as rheumatoid arthritis, experimental autoimmune encephalomyelitis (EAE), colitis, diabetes, and atherosclerosis. The invention thus provides pharmaceutical compositions comprising specific anti-eotaxin 2 antibodies for use alone or in combination with other therapeutic agents in the treatment of inflammatory, autoimmune and cardiovascular diseases. The invention also provides specific anti-eotaxin-2 monoclonal antibodies, and methods of treatment utilizing the antibodies of the invention.

Description

technical field [0001] The invention relates to the application of eotaxin-2 (CCL24) inhibitors in the treatment of inflammation, autoimmune diseases and cardiovascular diseases, especially the polyclonal or monoclonal anti-eotaxin-2 Antibody. Background technique [0002] Inflammatory chemokines are small cytokines that act as leukocyte chemokines, coordinating the balanced trafficking of cells in the body and the restoration of cell populations at sites of inflammation. Chemokine dysregulation has a broad role in diseases involving the human immune system including inflammatory and autoimmune diseases (1). [0003] The human eotaxin family includes 3 cytokine classes known to belong to the CC chemokine family: [0004] Eotaxin 1 (hypersensitive response eotaxin protein 1, also known as eotaxin or chemokine (C-C motif) ligand 11 (CCL11)) Known Selective recovery of eosinophils by induction of chemotaxis, involved in allergic responses. [0005] Eotaxin 2 (allergic respo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/24C07K14/52A61K39/00
CPCC07K16/24A61K2039/505A61K38/13A61K38/215A61P1/00A61P1/04A61P3/10A61P9/00A61P9/10A61P19/02A61P25/00A61P29/00A61P31/00A61P37/00A61P37/02A61K2300/00A61K39/395C07K14/52
Inventor J·乔治G·科伦
Owner 特拉维夫医学中心医学研究,基础设施及健康服务基金
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