Methods for treating type I diabetes mellitus by administering a soluble CTLA4 molecule
The present invention relates to compositions and methods for treating autoimmune diseases, such as diabetes, by administering to a subject a CTLA4 molecule that block endogenous B7 molecules from binding their ligands.
1. A method of treating autoimmune diseases in a subject comprising administering to the subject a CTLA4 molecule, wherein the CTLA4 molecule comprises:
(a) an amino acid sequence beginning with methionine at position +1 and ending with aspartic acid at position 124 of SEQ ID NO:17, or
(b) an amino acid sequence beginning with alanine at position −1 and ending with aspartic acid at position 124 of SEQ ID NO:17 and wherein said autoimmune disease is type I diabetes mellitus.
2. The method of claim 1 , wherein the extracellular domain of the CTLA4 molecule is joined to a non-CTLA4 molecule.
3. The method of claims 2 , wherein the non-CTLA4 molecule comprises an amino acid sequence which alters the solubility or affinity of the CTLA4 molecule.
4. The method of claim 3 , wherein the amino acid sequence which alters the solubility or affinity comprises an immunoglobulin moiety.
5. The method of claim 4 , wherein the immunoglobulin moiety is an immunoglobulin constant region or portion thereof.
6. The method of claim 5 , wherein the immunoglobulin constant region or portion thereof is mutated to reduce effector function.
7. The method of claim 6 , wherein the immunoglobulin constant region or portion thereof comprises a hinge, CH2 and CH3 regions of a human or monkey immunoglobulin molecule.
8. A method of treating autoimmune diseases in a subject comprising administering to the subject a CTLA4 molecule, wherein the CTLA4 molecule comprises:
(a) an amino acid sequence beginning with methionine at position +1 and ending with lysine at position 357 of SEQ ID NO:19, or
(b) an amino acid sequence beginning with alanine at position −1 and ending with lysine at position 357 of SEQ ID NO:19 and wherein said autoimmuine disease is type I diabetes mellitus.