Chimeric peptides comprising HER-2 B-cell epitopes and T-helper epitopes
View Patent ↗Compositions, methods, and vaccines that may stimulate the immune system and that may be used for treating malignancies associated with overexpression of the HER-2 protein are provided. Such compositions include epitopes of the HER-2 proteins.
1. An immunogenic composition comprising a chimeric peptide, wherein the chimeric peptide comprises a HER-2 B epitope, a T helper (Th) epitope, and a linker joining the HER-2 B epitope to the Th epitope, wherein:
the HER-2 B epitope consists of the sequence selected from the group consisting of:
SEQ ID NO: 2
CHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVA,;
SEQ ID NO: 3
VACAHYKDPPFCVA,;
SEQ ID NO: 4
VARCPSGVKPDLSYMPIWKFPDEEGACQPL,;
SEQ ID NO: 5
IWKFPDEEGACQPL,;
SEQ ID NO: 7
ACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEK,;
SEQ ID NO: 8
CPLHNQEVTAEDGTQRCEK,;
and
SEQ ID NO: 9
CPINCTHSCVDLDDKGCPAEQRAS,;
the Th epitope comprises the sequence selected from the group consisting of:
KLLSLIKGVIVHRLEGVE,;
SEQ ID NO: 10
NSVDDALINSTIYSYFPSV,;
SEQ ID NO: 11
PGINGKAIHLVNNQSSE,;
SEQ ID NO: 12
QYIKANSKFIGITEL,;
SEQ ID NO: 13
FNNFTVSFWLRVPKVSASHLE,;
SEQ ID NO: 14
LSEIKGVIVHRLEGV,;
SEQ ID NO: 15
FFLLTRILTIPQSLN,;
SEQ ID NO: 16
and
TCGVGVRVRSRVNAANKKPE,;
SEQ ID NO: 17
the linker comprises a sequence that is from 1 to 15 amino acids in length.
2. The composition according to claim 1 wherein at least one of the HER-2 B epitope, the Th epitope, or the linker is in retro-inverso form.
3. The composition according to claim 1 wherein the linker comprises 2 to 15 amino acids.
4. The composition according to claim 1 wherein the linker comprises GPSL, SEQ ID NO: 18.
5. The composition according to claim 1 wherein the Th epitope has the sequence of KLLSLIKGVIVHRLEGVE, SEQ ID NO: 10.
6. The composition according to claim 1 wherein the Th epitope has the sequence of NSVDDALINSTIYSYFPSV, SEQ ID NO: 11.
7. The composition according to claim 1 wherein the Th epitope has the sequence of PGINGKAIHLVNNQSSE, SEQ ID NO: 12.
8. The composition according to claim 1 wherein the Th epitope has the sequence of QYIKANSKFIGITEL, SEQ ID NO: 13.
9. The composition according to claim 1 wherein the Th epitope has the sequence of FNNFTVSFWLRVPKVSASHLE, SEQ ID NO: 14.
10. The composition according to claim 1 wherein the Th epitope has the sequence of LSEIKGVIVHRLEGV, SEQ ID NO: 15.
11. The composition according to claim 1 wherein the Th epitope has the sequence of FFLLTRILTIPQSLN, SEQ ID NO: 16.
12. The composition according to claim 1 wherein the Th epitope has the sequence of TCGVGVRVRSRVNAANKKPE, SEQ ID NO: 17.
13. The composition according to claim 1 further comprising a second HER-2 B epitope comprising the sequence selected from the group consisting of:
CHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVA, SEQ ID NO: 2;
VACAHYKDPPFCVA, SEQ ID NO: 3;
VARCPSGVKPDLSYMPIWKFPDEEGACQPL, SEQ ID NO: 4;
IWKFPDEEGACQPL, SEQ ID NO: 5;
LHCPALVTYNTDTFESMPNPEGRYTFGASCV, SEQ ID NO: 6;
ACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEK, SEQ ID NO: 7;
CPLHNQEVTAEDGTQRCEK, SEQ ID NO: 8; and
CPINCTHSCVDLDDKGCPAEQRAS, SEQ ID NO: 9.
14. The composition according to claim 13 further comprising a second linker joining the first HER-2 B epitope to the second HER-2 B epitope.
15. The composition according to claim 14 wherein the second linker comprises a sequence that is from 1 to 15 amino acids in length.
16. The composition according to claim 15 wherein the second linker comprises GPSL, SEQ ID NO: 18.
17. A method of stimulating an immune response in a subject comprising administering to said subject the composition of claim 1 .
18. A method of treating HER-2 expressing cancer in a subject comprising administering to said subject the composition of claim 1 .
19. The method according to claim 18 wherein the subject is a human and has one of the following cancers or a predisposition to one of the following cancers: breast cancer; ovarian cancer; lung cancer; prostate cancer; and colon cancer.
20. The method according to claim 19 wherein the cancer is breast cancer.