Prame derived peptides and immunogenic compositions comprising these
The invention relates to a peptide having a length of no more than 100 amino acids and comprising at least 19 contiguous amino acids from the amino acid sequence of the human PRAME protein, wherein the peptide comprises at least one HLA class II epitope and at least one HLA class I epitope from the amino acid sequence of the human PRAME protein and to its use as such or in a composition as a medicament for the treatment and/or prevention of cancer.
1. A method for the treatment of cancer in which the human PRAME protein is overexpressed, comprising administering to a subject in need thereof an immunogenic composition comprising peptides having a length between 33 and 35 contiguous amino acids from the amino acid sequence of human PRAME protein, wherein the peptide comprises at least one HLA class II epitope and at least one HLA class I epitope from the amino acid sequence of the human PRAME protein, and wherein the peptides are selected from the group consisting of SEQ ID Nos: 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, and 18.
2. The method according to claim 1 , wherein the cancer is selected from the group consisting of melanoma, lymphoma, papillomas, breast or cervical carcinomas, acute and chronic leukemias, medulloblastoma, non-small cell lung carcinoma, head and neck cancer, renal carcinoma, pancreatic carcinoma, prostate cancer, small cell lung cancer, multiple myeloma, sarcomas and hematological malignancies, chronic myeloid leukemia, and acute myeloid leukemia.
3. The method according to claim 1 , wherein the HLA class II epitope is capable of activating a CD4 + Th cell in human cancer patient and/or a healthy control.
4. The method according to claim 1 , wherein the HLA class II epitope is capable of activating a CD45RO positive CD4 + Th cell.
5. The method according to claim 1 , wherein the HLA class I epitope is C-terminally processed by proteasomal cleavage.
6. The method according to claim 5 , wherein the HLA class I epitope is capable of activating a CD8 + CTL in human cancer patient and/or in a healthy control.
7. The method according to claim 1 , wherein the contiguous amino acid sequence is selected from the group consisting of amino acid sequences SEQ ID NOs: 5, 6, 8, 14, 15, 16 and 18.
8. The method according to claim 1 , wherein the immunogenic composition further comprises at least one additional different peptide selected from the group consisting of SEQ ID Nos: 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, and 18.
9. The method according to claim 1 , wherein the composition further comprises at least one adjuvant.
10. The method according to claim 9 , wherein the adjuvant acts via a Toll-like receptor.