Amidated peptides and their deamidated counterparts displayed by hla-a*02 for use in immunotherapy against different types of cancers

Abstract

The invention relates to a peptide comprising an amino acid sequence selected from the group consisting of (i) SEQ ID NO: 1 to SEQ ID NO: 102, and (ii) a variant sequence thereof which maintains capacity to bind to MHC molecule(s) and/or induce T cells cross-reacting with said variant peptide, or a pharmaceutically acceptable salt thereof.

What is claimed is: 
     
         1 . A method of treating a patient who has uterine endometrial cancer, comprising administering to said patient a composition comprising activated T cells that kill cancer cells that present on the surface a peptide consisting of the amino acid sequence of YVWDRTELL (SEQ ID NO: 4). 
     
     
         2 . The method of  claim 1 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide 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. 
     
     
         3 . The method of  claim 1 , wherein the composition further comprises at least one immune stimulating cytokine selected from the group consisting of EOTAXIN, G-CSF, GM-CSF, INF-α, IFN-β, INF-γ, interleukin (IL)-1α, M-CSF, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-18, IL-15, IL-17, IP-10, MIP-2, KC, LIF, LIX, MCP-1, MIP-1α, MIP-1β, MIG, RANTES, TNFα, IL-12, VEGF, IL-9, and IL-21. 
     
     
         4 . The method of  claim 1 , further comprising administering to said patient at least one immune stimulating cytokine selected from the group consisting of EOTAXIN, G-CSF, GM-CSF, INF-α, IFN-β, INF-γ, interleukin (IL)-1α, M-CSF, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-18, IL-15, IL-17, IP-10, MIP-2, KC, LIF, LIX, MCP-1, MIP-1α, MIP-1β, MIG, RANTES, TNFα, IL-12, VEGF, IL-9, and IL-21. 
     
     
         5 . The method of  claim 3 , wherein the at least one immune stimulating cytokine is IL-2. 
     
     
         6 . The method of  claim 3 , wherein the at least one immune stimulating cytokine is IL-15. 
     
     
         7 . The method of  claim 3 , wherein the at least one immune stimulating cytokine is IL-21. 
     
     
         8 . The method of  claim 4 , wherein the at least one immune stimulating cytokine is IL-2. 
     
     
         9 . The method of  claim 4 , wherein the at least one immune stimulating cytokine is IL-15. 
     
     
         10 . The method of  claim 4 , wherein the at least one immune stimulating cytokine is IL-21. 
     
     
         11 . A method of eliciting an immune response in a patient who has uterine endometrial cancer, comprising administering to said patient a composition comprising activated T cells that kill cancer cells that present on the surface a peptide consisting of the amino acid sequence of YVWDRTELL (SEQ ID NO: 4). 
     
     
         12 . The method of  claim 11 , wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide 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. 
     
     
         13 . The method of  claim 11 , wherein the composition further comprises at least one immune stimulating cytokine selected from the group consisting of EOTAXIN, G-CSF, GM-CSF, INF-α, IFN-β, INF-γ, interleukin (IL)-1α, M-CSF, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-18, IL-15, IL-17, IP-10, MIP-2, KC, LIF, LIX, MCP-1, MIP-1α, MIP-1β, MIG, RANTES, TNFα, IL-12, VEGF, IL-9, and IL-21. 
     
     
         14 . The method of  claim 11 , further comprising administering to said patient at least one immune stimulating cytokine selected from the group consisting of EOTAXIN, G-CSF, GM-CSF, INF-α, IFN-β, INF-γ, interleukin (IL)-1α, M-CSF, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-18, IL-15, IL-17, IP-10, MIP-2, KC, LIF, LIX, MCP-1, MIP-1α, MIP-1β, MIG, RANTES, TNFα, IL-12, VEGF, IL-9, and IL-21. 
     
     
         15 . The method of  claim 13 , wherein the at least one immune stimulating cytokine is IL-2. 
     
     
         16 . The method of  claim 13 , wherein the at least one immune stimulating cytokine is IL-15. 
     
     
         17 . The method of  claim 13 , wherein the at least one immune stimulating cytokine is IL-21. 
     
     
         18 . The method of  claim 14 , wherein the at least one immune stimulating cytokine is IL-2. 
     
     
         19 . The method of  claim 14 , wherein the at least one immune stimulating cytokine is IL-15. 
     
     
         20 . The method of  claim 14 , wherein the at least one immune stimulating cytokine is IL-21. 
     
     
         21 . The method of  claim 1 , wherein the activated T cells are cytotoxic T cells produced by transducing T cells with a T cell receptor (TCR) that binds the peptide in a complex with an MHC class I molecule on the surface of the cancer cells. 
     
     
         22 . The method of  claim 11 , wherein the activated T cells are cytotoxic T cells produced by transducing T cells with a TCR that binds the peptide in a complex with an MHC class I molecule on the surface of the cancer cells.