Specific activation of a regulatory t cell and its use for treatment of asthma, allergic disease, autoimmune disease, graft rejection and for tolerance induction
AssigneeBoehringer Ingelheim International GmbH
InventorsFranz-Josef Schneider, Christian Becker, Tobias Bopp, Helmut Jonuleit, Edgar Schmitt
Life of this patent
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Abstract
The present invention relates specific activation of a regulatory T cell via a specific CD4 epitope and uses thereof, e.g. for the treatment of an autoimmune disease or an allergy or asthma or graft rejection or tolerance induction.
Claims79
1) A method for determining whether a substance which can interfere with the interaction of HIV-1 gp120 with CD4 can be useful for positively influence a disease in which increase of activated regulatory T cells (Treg cells) can improve clinical picture comprising:
- (a) providing a solution comprising a Treg cell,
- (b) adding a substance to be tested under conditions which allow interaction of the substance with a Treg cell,
- (c) measuring whether a Treg cell has been activated, wherein an activated Treg cell identifies the substance as a Treg cell activator.
15) A method for determining whether a Treg cell has been activated comprising:
- (a) providing a first solution comprising a Treg cell,
- (b) providing a second solution comprising a Treg cell,
- (c) manipulation the first solution by adding at least a test substance,
- (d) determining the amount of intracellular cAMP of the first and the second solution wherein an increased amount of intracellular cAMP of the first solution is indicative for an activated Treg cell.
16) A method for determining whether a substance can activate a Treg cell via interaction with the HIV-1 gp120-binding site of CD4, comprising:
- (a) pre-selecting a substance which can interact with the HIV-1 gp120-binding site of CD4,
- (b) providing a solution comprising a Treg cell,
- (c) adding a pre-selected substance according to (a) under conditions which allow interaction of the substance with a Treg cell,
- (d) measuring whether a Treg cell has been activated, wherein an activated Treg cell identifies the substance as a Treg cell activator.
34) A method for determining whether a substance can activate a regulatory T cell (Treg) via interaction with the epitope as set forth in SEQ ID NO:
- 1 comprising:
- (a) providing a first solution comprising a Treg cell,
- (b) adding a substance to be tested under conditions which allow interaction of the substance with a Treg cell,
- (c) measuring whether a Treg cell of the first solution has been activated,
- (d) providing a second solution comprising a Treg cell,
- (e) adding the substance to be tested and a peptide comprising an amino acid sequence as set forth in SEQ ID NO:
- 1 under conditions like (b),
- (f) measuring whether a Treg cell of the second solution has been activated,
- (g) comparing results obtained from (c) with those obtained from (f) wherein a reduced activation of (f) identifies the substance as a Treg cell activator which activates a Treg cell via interaction with the epitope as set forth in SEQ ID NO:
- 1.
51) Peptide spanning amino acid No. 1-31 of SEQ ID NO 1.
52) A Treg cell activator which activates Treg cell via interaction with the Treg cell epitope as set forth in SEQ ID NO:1.
57) (canceled)
58) A method for the treatment of a disease selected from a group consisting of (i) a non-autoimmune inflammatory disease:
- asthma, allergic asthma, respiratory allergy, allergic rhinoconjunctivitis, allergic alveolitis, contact allergy, atopic dermatitis, neurodermatitis, food allergy, graft-versus-host disease, non-autoimmune inflammatory bowel disease, acute respiratory distress syndrome, acute inflammatory pancreatitis, burns, wound healing, skin scarring disorders, sarcoidosis, Behcet's disease, Sweet's syndrome;
- (ii) an autoimmune inflammatory disease:
- rheumatoid arthritis, rheumatic fever, systemic lupus erythematosus, ulcerative colitis, Crohn's disease, autoimmune inflammatory bowel disease, diabetes type I, gastritis, autoimmune atrophic gastritis, autoimmune hepatitis, Hashimoto's thyroiditis, thyreoiditis, multiple sclerosis, myasthenia gravis, autoimmune haemolytic anemia, Addison's disease, scleroderma, Goodpasture's syndrome, Guillain-Barre syndrome, Graves' disease, glomerulonephritis, psoriasis, pemphigus vulgaris, pemphigoid, vitiligo, idiopathic leukopenia, Sjogren's syndrome, Wegener's granulomatosis;
- (iii) an inflammatory disease due to organ transplantation;
- (iv) a bone marrow transplantation;
- and (v) a disease due to exogenously administered self or exogenously administered non-autologous recombinant polypeptide which method comprises administering to a being in need of such a treatment a suitable amount of a pharmaceutical composition comprising at least one Treg cell activator.
65) (canceled)
67) A method for reducing or preventing an unwanted immune reaction due to a exogenously administered self or exogenously administered non-autologous recombinant polypeptide which method comprises administering to a being in need thereof a suitable amount of a pharmaceutical composition comprising a Treg cell activator.
73) Method for reducing or preventing an unwanted immune reaction comprising:
- (a) adding a sufficient amount of at least one Treg cell activator to a non-human animal, preferably a non-human primate.
74) A test system for determining whether a substance is a Treg cell activator comprising at least
- (a) a Treg cell and
- (b) a peptide comprising amino acid sequence as set forth in SEQ ID NO.:
- 1.
Dependencies are inferred from the claim text.