Combinations of modalities for the treatment of diabetes

Abstract

A method of treating, preventing, or delaying the progression of Type 1 diabetes mellitus by administering an effective amount of a fusion protein composition comprising a T-cell co-stimulation antagonist and a portion of an immunoglobulin molecule and an effective amount of a Type 1 diabetes autoantigen. The method includes, for example, administering a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) molecule and a Type 1 diabetes autoantigen. Pharmaceutical compositions are also provided herewith.

1 - 19 . (canceled) 
     
     
         20 . A pharmaceutical composition comprising:
 a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) fusion protein,   an autoantigen selected from the group consisting of: preproinsulin, GAD 65, ICA512/IA-2, HSP60, carboxypeptidase H, peripherin, and ganglioside or an immunologically active fragment or variant thereof, and   a pharmaceutically acceptable carrier.   
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein said CTLA4 fusion protein is abatacept. 
     
     
         22 . The pharmaceutical composition of  claim 20 , wherein said autoantigen is preproinsulin or an immunologically active fragment or variant thereof. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein said preproinsulin fragment is insulin B-chain or an immunologically active fragment or variant thereof. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein said insulin B-chain fragment comprises amino acids 33-47 of SEQ ID NO:1. 
     
     
         25 . The pharmaceutical composition of  claim 20 , wherein said pharmaceutically acceptable carrier is an oil-based carrier. 
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein said oil-based carrier is IFA or Montanide ISA. 
     
     
         27 . The pharmaceutical composition of  claim 20 , comprising about 250 mg to about 2000 mg of the fusion protein and about 0.5 to about 10 mg of the autoantigen.