Immunotherapy against several tumors including gastrointestinal and gastric cancer
The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 95 novel peptide sequences and their variants derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.
1. A fusion protein comprising a peptide consisting of the amino acid sequence selected from the group consisting of SYIIDPLNL (SEQ ID NO: 5), VWSDVTPLTF (SEQ ID NO: 6), NYLLYVSNF (SEQ ID NO: 7), VYTTSYQQI (SEQ ID NO: 8), HYKPTPLYF (SEQ ID NO: 9) and NYEETFPHI (SEQ ID NO: 15) and 80 N-terminal amino acids of an HLA-DR antigen-associated invariant chain (Ii).
2. A composition comprising
a peptide 1 consisting of the amino acid sequence selected from the group consisting of SYIIDPLNL (SEQ ID NO: 5), VWSDVTPLTF (SEQ ID NO: 6), NYLLYVSNF (SEQ ID NO: 7), VYTTSYQQI (SEQ ID NO: 8), and HYKPTPLYF (SEQ ID NO: 9) in the form of a pharmaceutically acceptable salt; and
an immunogenicity enhancing amount of at least one adjuvant.
3. The composition according to claim 2 , wherein the pharmaceutically acceptable salt is acetic acid or hydrochloric acid.
4. The composition according to claim 2 , wherein the at least one adjuvant is selected from the group consisting of imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, CpG oligonucleotides and derivates, poly-(I:C) and derivates, RNA, sildenafil, and particulate formations with PLG or virosomes.
5. The composition according to claim 2 , wherein the at least one adjuvant is selected from the group consisting of a colony-stimulating factor, imiquimod, resiquimod, and interferon-alpha.
6. The composition according to claim 2 , wherein the at least one adjuvant comprises imiquimod or resiquimod.
7. The composition of claim 2 , wherein said peptide is produced by solid phase peptide synthesis using a solid-phase support.
8. The composition of claim 7 , wherein said peptide is produced by the solid phase peptide synthesis using a solid-phase support followed by removal from the solid-phase support by a composition comprising 95% trifluoroacetic acid and a 50% scavenger mix.
9. The composition of claim 8 , wherein the trifluoroacetic acid is removed by evaporation.
10. The composition of claim 7 , wherein the peptide is purified using a method selected from the group consisting of re-crystallization, size exclusion chromatography, ion-exchange chromatography, hydrophobic interaction chromatography, and reverse-phase high performance liquid chromatography.
11. The composition of claim 10 , wherein the peptide is purified using ion-exchange chromatography using an organic or inorganic acid.
12. The composition of claim 11 , wherein the organic acid is selected from the group consisting of acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methane sulfonic acid, ethane sulfonic acid, p-toluenesulfonic acid, and salicylic acid, and the inorganic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid phosphoric acid.
13. The composition of claim 12 , wherein the organic acid is acetic acid or the inorganic acid is hydrochloric acid.
14. The composition of claim 10 , wherein the peptide is purified using ion-exchange chromatography using a base.
15. The composition of claim 14 , wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, and trimethylamine.
16. The composition of claim 2 , wherein the peptide is produced by a method comprising yeast cell or bacterial cell expression, wherein the peptide is subsequently isolated in the form of a pharmaceutically acceptable salt after yeast or bacterial cell expression.
17. The composition of claim 2 , further comprising a pharmaceutically acceptable carrier selected from the group consisting of saline, Ringer's solution, and dextrose solution.
18. The composition of claim 17 , further comprising a pharmaceutically acceptable excipient.