Peptides, combination of peptides and scaffolds for use in immunotherapeutic treatment of various 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 for the treatment of cancer, comprising administering to a subject in need thereof 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 ILSVVNSQL (SEQ ID NO: 323), wherein the peptide is in a complex with an MHC molecule, 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 consisting of the amino acid sequence of ILSVVNSQL (SEQ ID NO: 323) in a complex with an MHC 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, and 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.
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 derived 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 MHC 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 imiquimod, resiguimod, GM-CSP, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, CpG-containing oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, and particulate formations with poly(lactid co-glycolid) (PLG) and virosomes.
9. The method of claim 1 , 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 1 , further comprising stimulating the activated T cells in the presence of an anti-CD28 antibody and IL-12 to clonally expand the T cells.
12. The method of claim 1 , wherein the population of activated T cells comprises CD8-positive cells.
13. 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.
14. The method of claim 1 , wherein said cancer comprises glioblastoma.