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Epicutaneous immunorebalancing

An epidermal, autoimmune technique for use in an autoimmune, allergic or inflammatory disease, treating or preventing allergy, treating or alleviating an allergic, autoimmune or inflammatory disease in a subject, preventing or treating proliferative , to treat or alleviate proliferative, prophylactic areas present in subjects, to achieve the effect of avoiding onset or development, and improving recovery

Inactive Publication Date: 2016-11-23
DBV TECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, Bohle et al. describe that IL-10-producing Tregs are induced during early phases of SLIT but not maintained during later phases of SLIT

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Example 1: Epidermal Immunotherapy (EPIT) Induces CTLA-4+ Regulatory T Cells (Treg)

[0084] A. Materials and methods

[0085] Twenty BALB / c mice were orally sensitized to peanut protein extract with cholera toxin. After sensitization, 10 mice were treated by EPIT for 8 consecutive weeks or left untreated (sham). Ten unimmunized mice were included as controls. After the treatment period, mice were sacrificed and splenocytes were isolated for immunostaining and flow cytometry analysis or restimulation in vitro.

[0086] Splenocytes were stained with anti-mouse CD4, CD25, Foxp3, IL-10, CTLA-4, LAP antibodies. Cells were gated on CD4+ among lymphocytes identified by FSC / SSC and analyzed for percentage of LAP+, CD25+Foxp3+ or CD25+IL10+. Among lymphocytes identified by FSC / SSC, cells were gated on CD4+CD25+Foxp3+ and the percentage of cells expressing CTLA-4 was analyzed.

[0087] Splenocytes were restimulated by peanut protein extract alone or with anti-IL10 or anti...

Embodiment 2

[0092] Example 2: Continuous EPIT increases naive and effector Tregs

[0093] A. Materials and methods

[0094] Twenty BALB / c mice were orally sensitized to peanut protein extract with cholera toxin. After sensitization, 10 mice were treated by EPIT for 8 consecutive weeks or left untreated (sham). Ten unimmunized mice were included as controls. After the treatment period, mice were sacrificed and splenocytes were isolated for immunostaining and flow cytometry analysis.

[0095] Cells were gated on CD4+ in lymphocytes identified by FSC / SSC and analyzed for the percentage of CD25+Foxp3+CD44hiCD62L- (effector Tregs) or CD25+Foxp3+CD44loCD62L+ (naive Tregs).

[0096] Experiments were repeated twice.

[0097] B. Results

[0098] Foxp3+ Tregs induced by EPIT exhibit specific phenotypes: After EPIT, unimmunized (CD44lo / CD62L+) and effector (CD44hi / CD62-) Foxp3 Tregs were significantly increased ( Figure 4 ).

Embodiment 3

[0099] Example 3: Continuous EPIT increases natural and induced Treg

[0100] A. Materials and methods

[0101] Twenty BALB / c mice were orally sensitized to peanut protein extract with cholera toxin. After sensitization, 10 mice were treated by EPIT for 8 consecutive weeks or left untreated (sham). Ten unimmunized mice were included as controls. After the treatment period, mice were sacrificed and splenocytes were isolated for immunostaining and flow cytometry analysis.

[0102] Cells were gated on CD4+ in lymphocytes identified by FSC / SSC and analyzed for the percentage of CD25+Foxp3+CD304+ (nTreg) or CD25+Foxp3+CD304- (iTreg).

[0103] Experiments were repeated twice.

[0104] B. Results

[0105] After EPIT, both natural (CD304+) and induced (CD304-) Foxp3 Tregs were significantly increased ( Figure 5 ).

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Abstract

The present invention relates to compositions and methods for improving a subject condition by epicutaneous immunobalancing. The invention shows that particular regulatory T cells can be induced and maintained in a subject by epicutaneous treatment, thereby causing a substantial improvement in a subject condition. The invention may be used in a preventive context, to improve the immunobalance of a subject and avoid the onset or development of diseases, as well as in a therapeutic context, to improve a subject recovery. The invention is particularly suitable to prevent or treat aproliferative or autoimmune, disease. The invention may be used in any mammalian subject, preferably in human subjects, including children and adults.

Description

[0001] The present invention relates to compositions and methods for improving the condition of a subject through epidermal immune rebalancing. The present invention shows that a specific subset of regulatory T cells can be induced and maintained in a subject by epidermal treatment, resulting in a substantial improvement in the condition of the subject. The invention can be used in a prophylactic setting to improve the immune balance of a subject and avoid the onset or progression of disease, as well as in a therapeutic setting to improve a subject's recovery. The invention is particularly useful in the prevention or treatment of proliferative, autoimmune or inflammatory diseases, including allograft rejection. The invention may be used with any mammalian subject, preferably a human subject, including children and adults. Background of the invention [0002] Epicutaneous immunotherapy is a method of desensitizing allergic subjects by skin application of allergens. By applyin...

Claims

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Application Information

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IPC IPC(8): A61K39/35A61K35/17A61P29/00A61P37/08A61P37/02A61P35/00A61P3/10A61P37/06A61P1/00A61P11/06A61P25/00A61P19/02C12N5/0783
CPCA61K35/17A61K39/35C12N5/0637A61K2039/54A61P1/00A61P11/06A61P19/02A61P25/00A61P29/00A61P35/00A61P37/02A61P37/06A61P37/08A61P43/00A61P3/10A61K39/39A61K2039/55544A61K2039/57A61K2039/577
Inventor L.蒙杜莱特V.迪奥斯泽吉P.H.本哈默C.杜邦
Owner DBV TECH INC