Novel anti-CD98 antibody and use thereof

An antibody and antibody heavy chain technology, applied in the fields of diabetes therapeutics, rheumatoid arthritis therapeutics, and autoimmune disease therapeutics, can solve the problem that anticancer drugs have not yet been developed, and achieve the goal of curbing fatigue and exhaustion, and curbing the incidence of disease. and progress, the effect of fewer side effects

Inactive Publication Date: 2013-04-10
UNIVERSITY OF TOKUSHIMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far little work has been done on uses other than as anticancer agents

Method used

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  • Novel anti-CD98 antibody and use thereof
  • Novel anti-CD98 antibody and use thereof
  • Novel anti-CD98 antibody and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0141] (Example 1) Preparation of anti-mouse CD98 antibody

[0142] Bone marrow cells were isolated from BALB / c mice and cultured for 8 days in the presence of GM-CSF. Then, 8-week-old Wistar rats (1×10 7 cells). Two weeks after the first immunization, the immunization was repeated. Next, 2 weeks later, the mice were immunized again, and 3 days later, the spleens were removed from the rats. Using spleen cells and SP2 cells (myeloma cells), cell fusion was performed according to a conventional method, and selection was performed in HAT medium. Then, antibodies reactive to dendritic cells were selected using flow cytometry. For selected antibodies, single clones were collected by limiting dilution. Since the limiting dilution method was performed three times at 0.5 cells / well, the clones were considered to be single clones. No less than 40 kinds of antibodies can be isolated by the above method.

[0143] The obtained antibodies were added to a T cell culture system (a mix...

Embodiment 2

[0145] (Example 2) Reactivity of the anti-mouse CD98 antibody (mCD98Ab) of the present invention

[0146] In order to confirm the reactivity of the mCD98Ab of the present invention, CD98-expressing CHO cells (293T / CD98) were generated by introducing the mouse CD98 gene (mCD98, GenBank / EMBL / DDBJ Accession No. U25708). That is, pcDNA3.1 introduced with the mouse CD98 gene or pcDNA3.1 alone was transfected into CHO cells by electroporation. To select cells in which the CD98 gene was incorporated into the CHO cell genome, drug-resistant cells were isolated by performing drug screening using G418. Cells were stained with rat IgG (control antibody) or mCD98 Ab, washed to remove free antibody, and stained with PE-labeled anti-rat IgG. The result is as figure 2 shown. The mCD98Ab of the present invention does not react with cells without CD98 gene transfer, but reacts with cells with CD98 gene transfer. The left panel shows cells transfected with pcDNA3.1 alone, and the right pan...

Embodiment 3

[0148] (Example 3) Anti-inflammatory effect of the anti-mouse CD98 antibody (mCD98Ab) of the present invention

[0149] In order to evaluate the function of the mCD98Ab of the present invention, an OVA immunization model was prepared. That is, BALB / c mice were immunized and sensitized by subcutaneously injecting a complex of OVA (ovalbumin) protein mixed with complete Freund's adjuvant. Taking the first day of immunization and sensitization of mice as day 0, control antibody or anti-CD98 antibody (each 200 μg) was intraperitoneally administered to mice on day 2, 4, 6 and 8. On day 10, sera were isolated from mice, and OVA-specific IgM and IgG therein were measured by ELISA method. That is, ovalbumin was immobilized on a 96-well plate at a concentration of 50 µg / ml, and reacted with the collected serum. Anti-ovalbumin antibodies were detected with HRP-labeled anti-mouse IgG.

[0150] The result is as image 3 shown. exist image 3 Among them, a significant reduction in OV...

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Abstract

Disclosed is a novel therapeutic agent for autoimmune diseases, particularly type-1 diabetes and rheumatoid arthritis. A novel anti-CD98 antibody can be produced, and a novel therapeutic agent for autoimmune diseases (type-1 diabetes and rheumatoid arthritis) which relies on a novel mechanism of action can be provided using the antibody. The novel anti-CD98 antibody does not inhibit the transport of an amino acid by CD98. Further, unlike conventional anti-CD98 antibodies, the novel anti-CD98 antibody has activities such as an inhibitory activity on the activation of T-lymphocytes, an inhibitory activity on fibronectin-mediated cell adhesion, and an inhibitory activity on the production of an OVA antibody in an OVA-sensitized model.

Description

technical field [0001] The present invention relates to a novel anti-CD98 antibody, and further relates to a therapeutic agent for autoimmune diseases using the novel anti-CD98 antibody. More specifically, the present invention relates to a therapeutic agent for diabetes (especially type 1 diabetes) and a therapeutic agent for rheumatoid arthritis. Background technique [0002] CD98 is an approximately 120 kDa heterodimeric glycoprotein that is ubiquitously expressed on cell membranes and is thought to be involved in amino acid transport, cell fusion associated with increased membrane expression, and integrin-mediated adhesion. As the structure of CD98, it consists of about 80kDa type II transmembrane protein CD98hc (heavy chain: 4F2hc, SLC3A2) and six kinds of about 40kDa light chains (LAT1, LAT2, y+LAT1, y+LAT2, xCT, asc) One forms a heterodimer through disulfide bonds that functions as an amino acid transporter. The heavy chain (CD98hc) of CD98 functions to move the dim...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28A61K39/395A61P3/10A61P37/06C12N1/15C12N1/19C12N1/21C12N5/10C12N15/09C12P21/08
CPCA61K2039/505C07K16/2896C07K2317/73C07K2317/76A61P1/00A61P1/04A61P19/02A61P29/00A61P37/02A61P37/06A61P5/16A61P3/10
Inventor 安友康二
Owner UNIVERSITY OF TOKUSHIMA
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