Peptides and methods for the treatment of diabetes
The invention relates to peptides such as HCPYCSLQPLALEGSLQKRG [SEQ ID NO: 26] and their use in the treatment of type 1 diabetes and the generation of cytolytic CD4+ T cell.
1 . An in vitro method for the generation of a population of cytolytic CD4+ T cells against antigen presenting cells (APC) presenting insulin epitopes, comprising the steps of:
providing peripheral blood cells;
contacting said cells in vitro with an isolated immunogenic peptide comprising the amino acid sequence of HCXX[CST]SLQPLALEGSLQK [SEQ ID NO:7] or H[CST]XXCSLQPLALEGSLQK [SEQ ID NO:8] wherein X stands for any amino acid, and wherein the peptide has a length of between 12 and 50 amino acids; and
expanding said cells in the presence of IL-2.
2 . A pharmaceutical composition comprising (i) an immunogenic peptide comprising the amino acid sequence HCXX[CST]SLQPLALEGSLQK [SEQ ID NO: 7] or H[CST]XXCSLQPLALEGSLQK [SEQ ID NO:8] and (ii) a pharmaceutically acceptable carrier, wherein X stands for any amino acid, the immunogenic peptide has a length of between 12 and 50 amino acids, and the pharmaceutical composition is suitable for subcutaneous administration.
3 . The pharmaceutical composition according to claim 2 , wherein the immunogenic peptide comprises the amino acid sequence HCXXCSLQPLALEGSLQK [SEQ ID NO: 9], wherein X stands for any amino acid.
4 . The pharmaceutical composition according to claim 2 , wherein the immunogenic peptide consists of the amino acid sequence HCPYCSLQPLALEGSLQKRG [SEQ ID NO: 26].
5 . The pharmaceutical composition according to claim 2 , wherein the immunogenic peptide consists of the amino acid sequence HCXX[CST]SLQPLALEGSLQK [SEQ ID NO:7] or H[CST]XXCSLQPLALEGSLQK [SEQ ID NO:8], wherein X stands for any amino acid.
6 . The pharmaceutical composition according to claim 2 , wherein the immunogenic peptide consists of the amino acid sequence HCXXCSLQPLALEGSLQK [SEQ ID NO: 9], wherein X stands for any amino acid.
7 . A method of treating type 1 diabetes comprising subcutaneously administering to a subject in need thereof a therapeutically sufficient amount of an immunogenic peptide comprising the amino acid sequence of HCXX[CST]SLQPLALEGSLQK [SEQ ID NO:7] or H[CST]XXCSLQPLALEGSLQK [SEQ ID NO:8], wherein X stands for any amino acid, and wherein the peptide has a length of between 12 and 50 amino acids.
8 . The method of claim 7 , wherein the amino acid sequence comprises HCXXCSLQPLALEGSLQK [SEQ ID NO: 9], wherein X stands for any amino acid.
9 . The method of claim 7 , wherein the amino acid sequence consists of HCPYCSLQPLALEGSLQKRG [SEQ ID NO: 26].
10 . The method of claim 7 , wherein the amino acid sequence consists of HCXX[CST]SLQPLALEGSLQK [SEQ ID NO:7] or H[CST]XXCSLQPLALEGSLQK [SEQ ID NO:8], wherein X stands for any amino acid.
11 . The method of claim 7 , wherein the amino acid sequence consists of HCXXCSLQPLALEGSLQK [SEQ ID NO: 9], wherein X stands for any amino acid.