Chimeric peptides comprising HER-2 B-cell epitopes and Tcell helper epitopes
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 first and second chimeric peptide, wherein the first and second chimeric peptides 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 Th epitope comprises a 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;
the HER-2 B epitope of the first chimeric peptide consists of:
VARCPSGVKPDLSYMPIWKFPDEEGACQPL, SEQ ID NO: 4; and
the HER-2 B epitope of the second chimeric peptide consists of:
LHCPALVTYNTDTFESMPNPEGRYTFGASCV,
SEQ ID NO: 6.
2. The composition according to claim 1 wherein at least one of the HER-2 B epitope, the Th epitope, or the linker in at least the first chimeric peptide or second chimeric peptide is in retro-inverso form.
3. The composition according to claim 1 wherein the linker of at least one of the first chimeric peptide or second chimeric peptide comprises 2 to 15 amino acids.
4. The composition according to claim 1 wherein the linker of at least one of the first chimeric peptide or second chimeric peptide comprises GPSL, SEQ ID NO: 18.
5. The composition according to claim 1 wherein the Th epitope of at least one of the first chimeric peptide or second chimeric has a sequence of KLLSLIKGVIVHRLEGVE, SEQ ID NO: 10.
6. The composition according to claim 5 wherein the Th epitope of both the first chimeric peptide and second chimeric has a sequence of KLLSLIKGVIVHRLEGVE, SEQ ID NO: 10.
7. A method of stimulating an immune response in a subject comprising administering to said subject the composition of claim 1 .
8. A method of treating HER-2 expressing cancer in a subject comprising administering to said subject the composition of claim 1 .
9. The method according to claim 8 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.
10. The method according to claim 9 wherein the cancer is breast cancer.
11. An immunogenic composition comprising SEQ ID NO: 23.
12. A method of stimulating an immune response in a subject comprising administering to said subject the composition of claim 11 .
13. A method of treating HER-2 expressing cancer in a subject comprising administering to said subject the composition of claim 11 .
14. The method according to claim 13 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.
15. The method according to claim 14 wherein the cancer is breast cancer.
16. An immunogenic composition comprising SEQ ID NO: 21.
17. A method of stimulating an immune response in a subject comprising administering to said subject the composition of claim 16 .
18. A method of treating HER-2 expressing cancer in a subject comprising administering to said subject the composition of claim 16 .
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.