Method of treating with a peptide
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 for treating a patient who has cancer, comprising administering to the patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of SEQ ID NO: 378 or SEQ ID NO: 1,
wherein the peptide is in a complex with an MHC molecule,
wherein said cancer is selected from the group consisting of glioblastoma, breast cancer, colorectal cancer, renal cell carcinoma, chronic lymphocytic leukemia, hepatocellular carcinoma, non-small cell lung cancer, small cell lung cancer, Non-Hodgkin lymphoma, acute myeloid leukemia, ovarian cancer, pancreatic cancer, prostate cancer, esophageal cancer including cancer of the gastric-esophageal junction, gallbladder cancer and cholangiocarcinoma, melanoma, gastric cancer, testis cancer, urinary bladder cancer, head-and neck squamous cell carcinoma, and uterine cancer.
2. The method of claim 1 , wherein the T cells are autologous to the patient.
3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.
4. The method of claim 1 , wherein the activated T cells are produced by contacting T cells with the peptide loaded human class I or II MHC molecules expressed on the surface of an antigen-presenting cell for a period of time sufficient to activate the T cells.
5. The method of claim 1 , wherein the activated T cells are expanded in vitro.
6. The method of claim 1 , wherein the peptide is in a complex with the class I MHC molecule.
7. The method of claim 4 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.
8. The method of claim 7 , wherein the antigen presenting cell is a dendritic cell or a macrophage.
9. The method of claim 5 , wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.
10. The method of claim 1 , wherein the population of activated T cells comprises CD8-positive cells.
11. The method of claim 4 , wherein the contacting is in vitro.
12. The method of claim 1 , wherein the population of activated T cells are administered in the form of a composition.
13. The method of claim 12 , wherein the composition comprises an adjuvant.
14. The method of claim 13 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, 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.
15. The method of claim 1 , wherein the cancer is hepatocellular carcinoma.
16. The method of claim 1 , wherein the cancer is non-small cell lung cancer.
17. A method of eliciting an immune response in a patient who has cancer comprising administering to the patient a population of activated T cells that selectively recognize cancer cells that present a peptide consisting of the amino acid sequence of SEQ ID NO: 378 or SEQ ID NO: 1,
wherein the peptide is in a complex with an MEW molecule,
wherein said cancer is selected from the group consisting of glioblastoma, breast cancer, colorectal cancer, renal cell carcinoma, chronic lymphocytic leukemia, hepatocellular carcinoma, non-small cell and small cell lung cancer, Non-Hodgkin lymphoma, acute myeloid leukemia, ovarian cancer, pancreatic cancer, prostate cancer, esophageal cancer including cancer of the gastric-esophageal junction, gallbladder cancer and cholangiocarcinoma, melanoma, gastric cancer, testis cancer, urinary bladder cancer, head and neck squamous cell carcinoma, and uterine cancer.
18. The method of claim 17 , wherein the activated T cells are produced by contacting T cells with the peptide loaded human class I or II MHC molecules expressed on the surface of an antigen-presenting cell for a period of time sufficient to activate the T cells.
19. The method of claim 17 , wherein the cancer is hepatocellular carcinoma.
20. The method of claim 17 , wherein the cancer is non-small cell lung cancer.
21. The method of claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 378.
22. The method of claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.
23. The method of claim 17 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 378.
24. The method of claim 17 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.