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CD (cluster differentiation) 146 and application thereof to antibody diagnosis and treatment for inflammable diseases such as autoimmunity diseases

A technology for autoimmune diseases and inflammatory diseases, applied in the field of immunodiagnosis and biological therapy, can solve problems such as immune cell function defects, achieve the effects of reducing damage points and damage areas, preventing infiltration, and slowing down the onset and symptoms

Active Publication Date: 2013-01-09
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition to natalizumab (anti-α4β1 integrin), monoclonal antibodies that have been used clinically or entered clinical trials include rituximab (anti-CD20), alemtuzumab ( Alemtuzumab (anti-CD52), Daclizumab (anti-IL2R), these are antibodies against immune cells themselves, and the side effects directly caused by these antibodies are mainly the functional defects of immune cells, which in turn cause other immune cells. related diseases

Method used

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  • CD (cluster differentiation) 146 and application thereof to antibody diagnosis and treatment for inflammable diseases such as autoimmunity diseases
  • CD (cluster differentiation) 146 and application thereof to antibody diagnosis and treatment for inflammable diseases such as autoimmunity diseases
  • CD (cluster differentiation) 146 and application thereof to antibody diagnosis and treatment for inflammable diseases such as autoimmunity diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: Soluble CD146 is significantly increased in the cerebrospinal fluid of patients with multiple sclerosis

[0029] Adhesion molecules can be shed from endothelial cells under the stimulation of inflammatory factors. In order to detect the relationship between the level of soluble CD146 in cerebrospinal fluid and multiple sclerosis, we used ELISA to detect the cerebrospinal fluid of patients with multiple sclerosis and normal people. In soluble CD146, we found that soluble CD146 was significantly increased in CSF of patients with multiple sclerosis.

[0030] Main materials: cerebrospinal fluid of active multiple sclerosis patients (26 cases), normal human cerebrospinal fluid (22 cases), antibodies AA98, AA4, AA1, etc. The description is obtained.

[0031] Main reagents: 0.02M PB (pH 7.25), anti-CD146 antibody AA1, biotinylated anti-CD146 antibody AA98, streptavidin-HRP, TMB substrate (200ng / ml TMB, 0.03%H 2 o 2 , pH4.5)

[0032] Main method:

[0033] 1) Antib...

Embodiment 2

[0040] Example 2: Overexpression of CD146 on neovascularization in inflammatory diseases

[0041] In chronic inflammatory diseases, angiogenesis is an important pathological process, and a large number of adhesion molecules are involved in the process of angiogenesis. CD146 is an important angiogenesis-related adhesion molecule, and we have observed high expression of CD146 in various inflammatory disease tissues.

[0042] Main materials: spinal cord tissue of multiple sclerosis model mice, arthritic tissue of rheumatoid arthritis model rats. Clinical specimens come from brain tissue of normal people and patients with multiple sclerosis, human atherosclerosis exfoliated intimal tissue

[0043] Main reagents: OCT, 4% paraformaldehyde, xylene, absolute ethanol, absolute methanol, hydrogen peroxide, PBS, anti-CD146 antibody (rabbit anti-CD146, mouse anti-CD146 monoclonal antibody AA4)

[0044] Main methods: (1) Frozen section preparation: OCT was used to directly embed the spin...

Embodiment 3

[0057] Example 3: CD146 antibody inhibits inflammatory cells from crossing the human blood-brain barrier

[0058] The infiltration of inflammatory cells plays a very important role in the occurrence and development of inflammatory diseases. These inflammatory cells mainly include T cells, B cells, macrophages, neutrophils and so on. These cells exert anti-inflammatory and pro-inflammatory effects locally in tissues. The tissue damage is mainly caused by its inflammatory effect. Blocking the infiltration of inflammatory cells plays an important role in alleviating tissue damage. The migration and infiltration of inflammatory cells involves the regulation of a large number of adhesion molecules. The high expression of CD146 on vascular endothelial cells plays a very important role in the adhesion, rolling and migration of inflammatory cells. Anti-CD146 antibody AA98 can largely inhibit the effect of CD146 on inflammatory cell migration.

[0059] Using Transwell technology (L...

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Abstract

The invention relates to a CD (cluster differentiation) 146 and application thereof to antibody diagnosis and treatment for inflammable diseases such as autoimmunity diseases. The CD146 is a novel target for treating the inflammable diseases such as the autoimmunity diseases, and an antibody to the CD146 is a novel targeted drug for treating the diseases. Accordingly, the invention provides the CD146 or the antibody to the CD146 or functions and the form of the antibody in terms of application to preparing drugs for diagnosing and / or for treating the inflammable diseases. The function mechanism of the antibody to the CD146 in terms of treatment of the inflammable diseases (such as multiple sclerosis) mainly includes that inflammatory cells are stopped from penetrating through blood brain barriers and other vascular endothelial cell barriers of a patient, injury to myelin sheaths of the central nervous system and other relevant tissues of the patient caused by activated lymphocytes is further suppressed, accordingly, the progress and recurrence of the multiple sclerosis and injury to the relevant tissues are delayed, and symptoms of the multiple sclerosis and development of relevant inflammable diseases are relieved. Compared with a conventional glucocorticoid drug for treating the autoimmunity diseases, the antibody to the CD146 is low in side effect, and cannot cause injury to immune functions of the whole body of the patient.

Description

technical field [0001] The invention belongs to the field of immunodiagnosis and biotherapy. Specifically, the present invention relates to the application of CD146 molecule and its antibody in the diagnosis and treatment of inflammatory diseases. More specifically, the function of the CD146 monoclonal antibody AA98 and its functional form involved in the present invention is to block the adhesion, migration, and crossing of autoimmune cells and inflammatory cells to vascular endothelial cells, thereby blocking their own Immune cells and inflammatory cells kill the central nervous system and related tissues, thereby delaying and blocking the occurrence and development of autoimmune diseases and inflammatory diseases. Background technique [0002] Multiple sclerosis (MS) is an autoimmune disease affecting the brain and spinal cord, as well as an inflammatory disease that causes nerve demyelination and axonal damage. It is currently believed that activated lymphocytes crossi...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K47/48G01N33/577A61P29/00A61P25/28A61P19/02A61P9/10
Inventor 阎锡蕴罗永挺段红霞冯立群卢迪杨东玲冯静
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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