Peptides and combination of peptides for use in immunotherapy against pancreatic cancer and other cancers
The present invention relates to peptides, proteins, 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 T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
1. A method of treating cancer in a HLA-A*02+ patient, wherein said cancer comprises cancer cells that overexpress a LAMC2 polypeptide comprising the amino acid sequence of TLDGAAVNQV (SEQ ID NO: 22) and present at their surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence of TLDGAAVNQV (SEQ ID NO: 22), said method comprising administering to said patient an effective amount of activated antigen-specific CD8+ cytotoxic T cells to kill cancer cells, wherein said activated antigen-specific CD8+ cytotoxic T cells are produced by contacting in vitro CD8+ cytotoxic T cells with an antigen presenting cell presenting at its surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence of TLDGAAVNQV (SEQ ID NO: 22), wherein said cancer is selected from pancreatic cancer, esophageal cancer, uterine cancer, gallbladder cancer, and bile duct cancer.
2. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T cells autologous to the patient.
3. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T cells obtained from a healthy donor.
4. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T cells isolated from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.
5. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are expanded in vitro before being administered to the patient.
6. The method of claim 1 , wherein the cytotoxic T cells are expanded in vitro in the presence of an anti-CD28 antibody and IL-12.
7. The method of claim 1 , wherein the effective amount of activated antigen-specific CD8+ cytotoxic T cells to kill the cancer cells are administered in the form of a composition.
8. The method of claim 7 , wherein said composition further comprises an adjuvant.
9. The method of claim 8 , wherein said adjuvant is at least one selected from agonistic anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, interferon-alpha, interferon-beta, CpG oligonucleotides, poly-(I:C), RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.
10. The method of claim 1 , wherein the antigen presenting cell is a dendritic cell or a macrophage.
11. The method of claim 1 , wherein the antigen presenting cell is infected with a recombinant virus expressing a peptide consisting of the amino acid sequence of TLDGAAVNQV (SEQ ID NO: 22).
12. The method of claim 1 , wherein the cancer is pancreatic cancer.
13. The method of claim 1 , wherein the cancer is esophageal cancer.
14. The method of claim 1 , wherein the cancer is uterine cancer.
15. The method of claim 1 , wherein the cancer is gallbladder cancer.
16. The method of claim 1 , wherein the cancer is bile duct cancer.
17. The method of claim 9 , wherein the adjuvant comprises IL-2.
18. The method of claim 9 , wherein the adjuvant comprises IL-7.
19. The method of claim 9 , wherein the adjuvant comprises IL-15.
20. The method of claim 9 , wherein the adjuvant comprises IL-21.