Citrullinated antigen modified peptide and its application

A citrullinated, antigen-based technology, applied in the field of citrullinated antigen-modified peptides, can solve the problems of increased infection risk, expensive biological agents and small-molecule targeted drugs, and difficulty in controlling lesions in a targeted manner

Active Publication Date: 2020-10-09
PEOPLES HOSPITAL PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still some patients who do not respond well to the treatment
Biologics and small molecule targeted drugs are expensive, imposing a huge economic burden on patients and society
Moreover, these drugs do not act on the initial stage of the disease, and it is difficult to control the disease in a targeted manner.
Moreover, there are many adverse reactions such as bone marrow suppression, liver function damage, and increased risk of infection, resulting in many patients being unable to tolerate the treatment of these drugs

Method used

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  • Citrullinated antigen modified peptide and its application
  • Citrullinated antigen modified peptide and its application
  • Citrullinated antigen modified peptide and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] For the screening of citrullinated antigen-modified peptides, a total of 12 citrullinated antigen-modified peptides were designed, which are:

[0043] aVP1 (SEQ ID No. 6: SAVEL-Cit-SSVPGVR);

[0044] aVP2 (SEQ ID No. 7: SAVDL-Cit-SSVPGVR);

[0045] aVP3 (SEQ ID No. 3);

[0046] aVP4 (SEQ ID No. 8: SAVGL-Cit-SSVPGVR);

[0047] aVP5 (SEQ ID No. 4);

[0048] aVP6 (SEQ ID No. 9: SAVRL-Cit-FSVPGVR);

[0049] aVP7 (SEQ ID No. 10: SAVRL-Cit-SSVEGVR);

[0050] aVP8 (SEQ ID No. 11: SAVRL-Cit-SSVKGVR);

[0051] aVP9 (SEQ ID No. 12: SAVRL-Cit-SSVWGVR);

[0052] aVP10 (SEQ ID No. 13: SAVEL-Cit-WSVPGVR);

[0053] aVP11 (SEQ ID No. 14: SAVDL-Cit-SSVRGVR);

[0054] aVP12 (SEQ ID No. 15: SAVAL-Cit-KSVFGVR);

[0055]Prototype peptide (SEQ ID No. 16: SAVRL-Cit-SSVPGVR).

[0056] according to figure 1 It can be seen that under the stimulation of the prototype peptide, the level of IL-6 produced by peripheral blood PBMCs of patients with rheumatoid arthritis increases. However,...

Embodiment 2

[0062] Hyporesponsiveness of citrullinated antigen-modified peptides in peripheral blood T cells of patients with rheumatoid arthritis.

[0063] In an embodiment of the present invention, the reactivity of peripheral blood T cells of patients with rheumatoid arthritis to two citrullinated antigen-modified peptides, aVP3 and aVP5, was studied, and the expression of the inflammatory cytokine IL-6 stimulated by the allosteric peptide was detected. produce level changes.

[0064] Starting with 4 mL of each patient's blood, blood was added to 4 mL of Ficoll-Paque PLUS in a 15 mL centrifuge tube that was centrifuged at 1200 rpm for 30 minutes. Extract the corresponding mononuclear cell (PBMC) layer. Subsequently, the cells were washed twice with 15 mL of 1×PBS, and they were centrifuged at 1200 rpm after each wash. Finally, the cell pellet was resuspended in RPMI1640 containing 10% fetal bovine serum plus penicillin (100 U / mL), streptomycin (100 μg / mL), 25 mM / L HEPES and 2 mM L-gl...

Embodiment 3

[0070] Therapeutic effects of aVP3 and aVP5 allosteric peptides were evaluated in an animal model of bovine type II collagen (CII)-induced arthritis.

[0071] In this example, an irrelevant peptide (iP) was added in addition to wVP, aVP3 and aVP5. The peptide segment of the irrelevant peptide is the reverse sequence Myr-RVGPVSS-Cit-LRVAS (SEQ ID No. 5) of wVP.

[0072] The experimental arthritis model in the present invention adopts the internationally recognized collagen-induced arthritis (CIA) model. The experimental animals were inbred DBA / 1 mice. The mice used in this experiment were from Beijing Huafukang Biotechnology Co., Ltd. All mice were raised in the Animal Experiment Center (SPF level) of Peking University People's Hospital. All experimental mice were male mice aged 6-8 weeks. All procedures involving animals in the experiment were carried out in accordance with the regulations on the management of experimental animals in my country.

[0073] Purchase bovine t...

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PUM

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Abstract

The present invention provides a citrullinated antigen-modified peptide and an application thereof, and relates to the technical field of rheumatoid arthritis treatment. The citrullinated antigen-modified peptide has an amino acid sequence shown in SEQ ID No.1 or SEQ ID No.2. The citrullinated antigen-modified peptide specifically binds to rheumatoid arthritis-related HLA-DRB1 to inhibit binding of an antigen peptide to the HLA-DRB1, thus activation of T cells is inhibited and a purpose of treating rheumatoid arthritis is achieved.

Description

technical field [0001] The invention relates to the technical field of treating rheumatoid arthritis, in particular to citrullinated antigen-modified peptides and applications thereof. Background technique [0002] Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic progressive joint disease. Lesions mainly accumulate in multiple joints of the whole body, showing multiple and symmetrical chronic synovitis, which in turn causes cartilage and bone destruction, and severe cases can lead to joint deformities and even disability. Rheumatoid arthritis is one of the major diseases causing loss of work force and disability. [0003] The etiology of rheumatoid arthritis is not yet clear, but it is generally believed that genetic factors play an important role in the pathogenesis of rheumatoid arthritis. Recent studies on the pathogenesis of rheumatoid arthritis have shown that autoantigen-driven T cell activation is the basis for the pathogenesis and evol...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08A61K38/10A61P19/02
CPCA61K38/00A61P19/02C07K7/08
Inventor 栗占国孙晓麟刘佳佳来鲁华梁浩
Owner PEOPLES HOSPITAL PEKING UNIV
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