Method for treating cancer with activated T cells
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 treatment of a patient with cancer, comprising administering to the patient a composition comprising a population of activated T cells that selectively recognize cancer cells that aberrantly express a peptide consisting of the amino acid sequence of RLLPKVQEV (SEQ ID NO: 325), wherein the peptide is in a complex with an MHC molecule, wherein said cancer is selected from the group consisting of glioblastoma, colorectal cancer, renal cell carcinoma, chronic lymphocytic leukemia, hepatocellular carcinoma, non-small cell and small cell lung cancer, Non-Hodgkin lymphoma, acute myeloid leukemia, 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 T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.
5. The method of claim 1 , further comprising expanding T cells in vitro.
6. The method of claim 1 , wherein the WIC molecule is a class I molecule.
7. The method of claim 1 , wherein the composition further comprises an adjuvant.
8. The method of claim 7 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiguimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG-containing oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, and particulate formations 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.
9. The method of claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells, in vitro, with an antigen presenting cell that expresses the peptide in a complex with an MEW class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell specifically against the peptide.
10. The method of claim 9 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.
11. The method of claim 10 , wherein the antigen presenting cell is a dendritic cell or a macrophage.
12. The method of claim 9 , further comprising stimulating the activated T cells in the presence of an anti-CD28 antibody and IL-12 to clonally expand the T cells.
13. The method of claim 1 , wherein the population of activated T cells comprises CD8-positive cells.
14. The method of claim 1 , wherein the peptide is present in the cancer cells at a level at least 1.2-fold of that present in normal tissue.