Method for treating cancer with an activated T lymphocyte that selectively recognizes a cancer cell consisting of specific 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 the treatment of a patient who has cancer, comprising administering to the patient a population of activated T lymphocytes that selectively recognizes cancer cell, which presents a peptide consisting of the amino acid sequence of SEQ ID NO: 8,
wherein the peptide is in a complex with an MEW molecule,
wherein said cancer is selected from the group consisting of ovarian cancer, non-small cell lung cancer, small cell lung cancer, kidney cancer, brain cancer, colon or rectum cancer, stomach cancer, liver cancer, pancreatic cancer, prostate cancer, leukemia, breast cancer, Merkel cell carcinoma, melanoma, esophageal cancer, urinary bladder cancer, uterine cancer, gallbladder cancer, and bile duct cancer.
2. The method of claim 1 , wherein the activated T lymphocytes are produced by a method comprising contacting in vitro T cells with the peptide loaded human class I or II MHC molecules expressed on the surface of an antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a period of time sufficient to activate said T cells.
3. The method of claim 1 , wherein said cancer is ovarian cancer.
4. The method of claim 1 , wherein the T lymphocytes are autologous to the patient.
5. The method of claim 1 , wherein the T lymphocytes are obtained from a healthy donor.
6. The method of claim 1 , wherein the T lymphocytes are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.
7. The method of claim 1 , wherein the activated T lymphocytes are expanded in vitro.
8. The method of claim 1 , wherein the MHC molecule is a class I MHC molecule.
9. The method of claim 2 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.
10. The method of claim 9 , wherein the antigen presenting cell is a dendritic cell or a macrophage.
11. The method of claim 7 , wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.
12. The method of claim 1 , wherein the population of activated T lymphocytes comprises CD8-positive cells.
13. The method of claim 1 , wherein the population of activated T lymphocytes are administered in the form of a composition.
14. The method of claim 13 , wherein the composition comprises an adjuvant.
15. The method of claim 14 , 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 derivates, poly-(I:C) and derivates, RNA, sildenafil, particulate formulations with poly(lactid co-glycolid) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.
16. The method of claim 14 , wherein the adjuvant comprises IL-21.
17. The method of claim 1 , wherein the cancer is ovarian cancer.
18. The method of claim 1 , wherein the cancer is melanoma.
19. The method of claim 1 , wherein the cancer is urinary bladder cancer.
20. The method of claim 1 , wherein the cancer is uterine cancer.