Methods and compounds for eliminating immune responses to therapeutic agents
The invention describes kit of parts of polypeptides comprising: a) a peptide comprising: a1) an MHC class II T cell epitope or a CD1 d-restricted NKT cell epitope, and a2) immediately adjacent to said epitope or separated by at most 7 amino acids from said epitope a [CST]-X(2)-C [SEQ ID NO:7] or C-X(2)-[CST] [SEQ ID NO:8] oxidoreductase motif sequence, and b) a polypeptide comprising: b1) a therapeutic protein and b2) the epitope defined in a1), wherein the epitope sequence is a sequence which differs from the sequence of the protein of b1). The therapeutic protein, in combination with the peptide, is used to prevent an immune response against the therapeutic protein.
1. A kit of parts of polypeptides comprising:
a) a peptide comprising:
a1) a first peptide sequence comprising an MHC class II T cell epitope, and
a2) immediately adjacent to said first peptide sequence or separated by at most 7 amino acids from said first peptide sequence a [CST]-X(2)-C [SEQ ID NO:7] or C-X(2)-[CST] [SEQ ID NO:8] oxidoreductase motif sequence, and
b) a fusion polypeptide comprising as fusion partners:
b1) a therapeutic protein and
b2) the first peptide sequence defined in al), wherein the first peptide sequence does not occur in the sequence of the protein of b1).
2. The kit of parts according to claim 1 , wherein the oxidoreductase motif sequence is C-X(2)-C [SEQ ID NO: 2].
3. The kit of parts according to claim 1 , wherein said MHC class II T cell epitope is a promiscuous epitope binding to one or more HLA-DR1 molecules.
4. The kit of parts according to claim 1 , wherein said MHC class II T cell epitope has the sequence X 1 X 2 MATX 6 LLM [SEQ ID NO: 29], wherein X 1 and X 2 are independently selected from V, I, L, M, Y, H, F and W, and X 6 is R or P.
5. A method of reducing the clearance of the fusion polypeptide of claim 1 b) caused by antigen presentation by antigen-presenting cells in an individual, comprising administering to said individual
a) an effective amount of the peptide of claim 1 a); and
b) the fusion polypeptide of claim 1 b) or a polynucleotide encoding the fusion polypeptide of claim 1 b).
6. The method according to claim 5 , wherein step b) comprises administering the fusion polypeptide of claim 1 b).
7. A method for preparing a kit of parts of polypeptides according to claim 1 , comprising:
i) preparing the polypeptide of b),
ii) preparing the peptide of a), and
iii) placing the polypeptide of b) and peptide of a) in a kit.
8. A method comprising administering to a subject in need thereof an effective amount of
a) the peptide of claim 1 a); and
b) the fusion polypeptide of claim 1 b) or a polynucleotide encoding the fusion polypeptide of claim 1 b), wherein the therapeutic protein is an antibody, coagulation factor, fibrinolytic peptide, hormone, cytokine or growth factor.
9. The method according to claim 8 , wherein step b) comprises administering the fusion polypeptide of claim 1 b).
10. The method according to claim 8 , wherein the therapeutic protein is an antibody.
11. The method according to claim 8 , wherein the therapeutic protein is a coagulation factor.
12. The method according to claim 8 , wherein the therapeutic protein is a growth factor.