Peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) and other cancers
A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), in which the peptide is in a complex with an MHC molecule.
1. A method of eliciting a CD8+ cytotoxic T cell response in an HLA-A*02+ patient who has hepatocellular carcinoma (HCC), comprising
identifying the patient who has HCC cells that over-present on the cell surface a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) as compared to a panel of normal tissues, wherein the peptide is in a complex with HLA-A*02, and
administering to said identified patient a composition comprising a population of activated antigen-specific CD8+ cytotoxic T cells to kill the HCC cells in the identified patient,
wherein the population of activated antigen-specific CD8+ cytotoxic T cells recognize the HCC cells by interacting through their TCR with a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) in a complex with HLA-A*02 presented at the surface of the HCC cells.
2. The method of claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are autologous to the patient.
3. The method of claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are obtained from a healthy donor.
4. The method of claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.
5. The method of claim 1 , wherein the composition further comprises an adjuvant.
6. The method of claim 5 , 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.
7. A method of eliciting a CD8+ cytotoxic T cell response in an HLA-A*02+ patient who has hepatocellular carcinoma (HCC), wherein the HCC cells overexpress a MAGEB2 polypeptide comprising the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) as compared to a panel of normal tissues, wherein the HCC cells present at the cell surface a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) in a complex with HLA-A*02, comprising
isolating CD8+ cytotoxic T cells,
contacting the CD8+ cytotoxic T cells with an antigen presenting cell that present at the cell surface a peptide consisting of SEQ ID NO. 303 in a complex with HLA-A*02 in vitro, thereby activating the CD8+ cytotoxic T cells, and
administering to said patient who has HCC a composition comprising a population of the activated antigen-specific CD8+ cytotoxic T cells to kill the HCC cells in the patient,
wherein the population of the activated antigen-specific CD8+ cytotoxic T cells recognize the HCC cells by interacting through their TCR with a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303) in a complex with HLA-A*02 presented at the surface of the HCC cells.
8. The method of claim 7 , further comprising expanding the activated T cells in vitro.
9. The method of claim 7 , wherein the composition further comprises an adjuvant.
10. The method of claim 9 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, OM-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.
11. The method of claim 7 , wherein the antigen presenting cell in a dendritic cell or a macrophage.
12. The method of claim 8 , wherein the expanding is in the presence of an anti-CD28 antibody and IL-12.