AGENT FOR THE TREATMENT AND OR PROPHYLAXIS OF AN AUTOIMMUNE DISEASE AND FOR THE FORMATION OF REGULATORY T CELLS
The present invention relates to an agent for the treatment and/or prophylaxis of an autoimmune disease, an agent for the formation of regulatory T cells (T Reg ) in an organism and various methods in which the agents according to the invention are used.
1 . (canceled)
2 . A method for inducing regulatory T cells in a cell population of an organism, the method comprising:
contacting a cell population of an organism with a mutein of human interleukin-2 (hIL-2 mutein) or a fragment thereof, wherein said hIL-2 mutein has an amino acid substitution in at least one of the positions 20, 88 or 126, numbered in accordance with the hIL-2 wild type sequence as set forth in SEQ ID NO: 1,
wherein regulatory T cells are induced in the cell population of the organism.
3 . The method of claim 2 , wherein in said hIL-2 mutein or fragment thereof, through the substitution at position 88, an asparagine is exchanged for an amino acid which is selected from the group consisting of: arginine (hIL-2-N88R), glycine (hIL-2-N88G), or isoleucine (hIL-2-N88I).
4 . The method of claim 3 , wherein said hIL-2 mutein or fragment thereof has at least one further amino acid substitution in any position except the positions 20, 88, or 126, so that the thus further substituted hIL-2 mutein or fragment thereof has an amino acid sequence which is at least about 80% identical with the amino acid sequence of the hIL-2 mutein or fragment thereof which is not further substituted.
5 . The method of claim 4 , wherein the further substituted hIL-2 mutein or fragment thereof exhibits at least about 80% of the activity for inducing regulatory T cells of the hIL-2 mutein or fragment thereof before the further substitution.
6 . The method of claim 4 , wherein the at least one further substitution is a conservative amino acid substitution.
7 . The method of claim 2 , wherein in said hIL-2 mutein or fragment thereof, through the substitution at position 20, an aspartic acid is exchanged for an amino acid which is selected from the group consisting of: histidine (hIL-2-D20H), isoleucine (hIL-2-D20I), or tyrosine (hIL-2-D20Y).
8 . The method of claim 7 , wherein said hIL-2 mutein or fragment thereof has at least one further amino acid substitution in any position except the positions 20, 88, or 126, so that the thus further substituted hIL-2 mutein or fragment thereof has an amino acid sequence which is at least about 80% identical with the amino acid sequence of the hIL-2 mutein or fragment thereof which is not further substituted.
9 . The method of claim 8 , wherein the further substituted hIL-2 mutein or fragment thereof exhibits at least about 80% of the activity for inducing regulatory T cells of the hIL-2 mutein or fragment thereof before the further substitution.
10 . The method of claim 8 , wherein the at least one further substitution is a conservative amino acid substitution.
11 . The method of claim 2 , wherein in said hIL-2 mutein or fragment thereof, through the substitution at position 126, a glutamine is exchanged for a leucine (hIL-2-Q126L).
12 . The method of claim 11 , wherein said hIL-2 mutein or fragment thereof has at least one further amino acid substitution in any position except the positions 20, 88, or 126, so that the thus further substituted hIL-2 mutein or fragment thereof has an amino acid sequence which is at least about 80% identical with the amino acid sequence of the hIL-2 mutein or fragment thereof which is not further substituted.
13 . The method of claim 12 , wherein the further substituted hIL-2 mutein or fragment thereof exhibits at least about 80% of the activity for inducing regulatory T cells of the hIL-2 mutein or fragment thereof before the further substitution.
14 . The method of claim 12 , wherein the at least one further substitution is a conservative amino acid substitution.
15 . The method of claim 2 , wherein the method further comprises administering to the organism an immunosuppressant.
16 . The method of claim 15 , wherein the immunosuppressant is selected from the group consisting of: glucocorticoid, including decortin, prednisol; azathioprine; cyclosporin A; tacrolimus; an anti-T lymphocyte globulin; an anti-CD3 antibody; muromonab; an anti-CD25 antibody; basiliximab; daclizumab; an anti-TNF-α antibody; infliximab; adalimumab; azathioprine; methotrexate; cyclosporin; sirolimus; everolimus; fingolimod; CELLCEPT® (mycophenolate mofetil); myfortic; and cyclophosphamide.
17 . The method of claim 2 , wherein the organism is in need of treatment, prophylaxis, and/or prevention of the worsening of an autoimmune disease.
18 . The method of claim 17 , wherein the autoimmune disease is type I diabetes, multiple sclerosis, or systemic lupus erythematosus (SLE).
19 . The method of claim 2 , wherein the organism is human.
20 . The method of claim 2 , wherein the regulatory T cells are induced in vitro.
21 . The method of claim 2 , wherein the regulatory T cells are induced in vivo.