Immunogenic control of tumours and tumour cells

1. An isolated immunogenic peptide for eliciting non-viral tumor associated antigen-specific CD4+ T cells, which are cytotoxic for tumor cells, said immunogenic peptide comprising:

(i) an MHC class II T-cell epitope consisting of an amino acid sequence of a non-viral tumor associated antigen comprising at least eight amino acids, wherein said CD4+ T cells recognize the T-cell epitopes bound to MHC class II molecules presented on the tumor cells; and

(ii) a redox motif consisting of C-(X)2-[CST] (SEQ ID NO: 21) or [CST]-(X)2-C (SEQ ID NO: 22), which is immediately adjacent to the T-cell epitope or separated from the T-cell epitope by a linker of at most 7 amino acids in said peptide;

wherein said non-viral tumor associated antigen comprises the amino acid sequence with the proviso that neither C-X(2)-[CST] (SEQ ID NO: 21) nor [CST]-(X)2-C (SEQ ID NO: 22) is within 11 amino acids N-terminally or C-terminally of the amino acid sequence in the non-viral tumor associated antigen.

2. The peptide according to claim 1 , wherein said non-viral tumor associated antigen is selected from the group consisting of oncogenes, proto-oncogenes, surviving factors, clonotypic determinants, and idiotypic determinants.

3. The peptide according to claim 1 , wherein said non-viral tumor associated antigen is an oncogene or proto-oncogene.

4. The peptide according to claim 1 , wherein the motif is C-(X)2-C (SEQ ID NO: 23).

5. The peptide according to claim 1 , which has a length up to 50 amino acids.

6. The peptide according to claim 1 , wherein the linker has a length of at most 4 amino acids.

7. The peptide according to claim 1 , which further comprises an endosomal targeting sequence.

8. The peptide according to claim 1 , wherein at least one X in said motif is Gly, Ala, Ser or Thr.

9. The peptide according to claim 1 , wherein at least one X in said motif is His or Pro.

10. The peptide according to claim 1 , wherein at least one C in said motif is methylated.

11. A method for obtaining a population of CD4+ T cells which are cytotoxic for antigen presenting cells presenting a non-viral tumor associated antigen, the method comprising the steps of:

providing peripheral blood cells;

contacting said cells in vitro with an effective amount of the immunogenic peptide of claim 1 ;

and

expanding said cells in the presence of Interleukin 2 (IL-2).

12. A method for obtaining a population of CD4+ T cells which are cytotoxic for antigen presenting cells presenting a non-viral tumor associated antigen from a subject, the method comprising the steps of:

administering an effective amount of the immunogenic peptide of claim 1 to said subject; and

obtaining said population of cytotoxic CD4+ T cells from said subject.

13. The method according to claim 11 , wherein said tumor non-viral associated antigen is selected from the group consisting of oncogenes, proto-oncogenes, surviving factors, clonotypic determinants, and idiotypic determinants.

14. The method according to claim 11 , wherein said non-viral tumor associated antigen is an oncogene or proto-oncogene.

15. The method according to claim 12 , wherein said tumor non-viral associated antigen is selected from the group consisting of oncogenes, proto-oncogenes, surviving factors, clonotypic determinants, and idiotypic determinants.

16. The method according to claim 12 , wherein said non-viral tumor associated antigen is an oncogene or proto-oncogene.

17. A method of treating a tumor expressing a non-viral tumor associated antigen or of treating a relapse of a tumor expressing a non-viral tumor associated antigen in a subject in need thereof comprising:

administering a therapeutically effective amount of the immunogenic peptide of claim 1 to the subject.

18. The method according to claim 17 , wherein said non-viral tumor associated antigen is selected from the group consisting of oncogenes, proto-oncogenes, surviving factors, clonotypic determinants, and idiotypic determinants.

19. The method according to claim 17 , wherein said non-viral tumor associated antigen is an oncogene or proto-oncogene.

20. A method of producing the isolated immunogenic peptide of claim 1 comprising the steps of:

identifying an MHC class II T cell epitope in a protein sequence of a non-viral tumor associated antigen, wherein said non-viral tumor associated antigen does not comprise in its sequence C-(X)2-[CST] (SEQ ID NO: 21) or [CST]-(X)2-C (SEQ ID NO: 22) within 11 amino acids N-terminally or C-terminally of said T-cell epitope in the non-viral tumor associated antigen; and

producing the peptide.

21. The method according to claim 20 , wherein said non-viral tumor associated antigen is selected from the group consisting of oncogenes, proto-oncogenes, surviving factors, clonotypic determinants, and idiotypic determinants.

22. The method according to claim 20 , wherein said non-viral tumor associated antigen is an oncogene or proto-oncogene.

23. The peptide according to claim 1 , wherein the motif is C-(X)2-C (SEQ ID NO: 23), the tumor-associated antigen has a natural sequence, and C-(X)2-C does not occur within 11 amino acids N-terminally or C-terminally of the T-cell epitope in the natural sequence of the tumor-associated antigen.

24. The peptide according to claim 1 , wherein the tumor-associated antigen has a natural sequence, and C-(X)2-[CST] (SEQ ID NO: 21) or [CST]-(X)2-C (SEQ ID NO: 22) does not occur within 11 amino acids N-terminally or C-terminally of the T-cell epitope in the natural sequence of the tumor-associated antigen.

25. The peptide according to claim 1 , wherein the motif is C-(X)2-C (SEQ ID NO: 23), the tumor-associated antigen has a natural sequence, and C-(X)2-C (SEQ ID NO: 23) does not occur in the natural sequence of the tumor-associated antigen.

26. The peptide according to claim 1 , wherein the tumor-associated antigen has a natural sequence, and C-(X)2-[CST] (SEQ ID NO: 21) or [CST]-(X)2-C (SEQ ID NO: 22) does not occur in the natural sequence of the tumor-associated antigen.