Identification of mhc class i phospho-peptide antigens from breast cancer utilizing shla technology and complementary enrichment strategies

Abstract

The present invention describes novel tumor-specific phosphorylated peptides, nucleic acids encoding those peptides, and antibodies generated against said peptides. The genes, peptides, and antibodies described herein may be used as diagnostic indicators of the presence of breast cancer and/or used in therapeutics to treat breast cancer.

1 . An isolated phosphopeptide of 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acids comprising a sequence selected from the group consisting of SEQ ID NOs: 70-171 or a sequence at least 90% identical thereto. 
     
     
         2 . The isolated phosphopeptide of  claim 1 , wherein said sequence is selected from group consisting of SEQ ID NOs: 84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165 or a sequence of at least 90% identical thereto. 
     
     
         3 . The isolated phosphopeptide of  claim 1 , wherein said sequence is selected from the group consisting of SEQ ID NOs: 118, 121, 132, 145, 164, and 165 or a sequence of at least 90% identical thereto. 
     
     
         4 . A composition comprising one or more phosphopeptides of  claim 1  and a pharmaceutically acceptable carrier wherein the number is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30. 
     
     
         5 . The composition of  claim 4 , wherein said composition has the ability to stimulate a T cell mediated immune response to at least one of said phosphopeptides. 
     
     
         6 . The composition of  claim 4 , comprising a peptide capable of binding to the HLA-B*0702 allele on the WIC class I molecule. 
     
     
         7 . The composition of  claim 4 , wherein the composition is capable of increasing the 5-year survival rate of breast cancer patients treated with the composition relative to average 5-year survival rates that could have been expected without treatment with the composition. 
     
     
         8 . The composition of  claim 1 , wherein said composition comprises one or more phosphopeptides comprising a sequence selected from the group consisting of SEQ ID NOs: 84, 87, 96, 102, 118, 121, 125, 126-, 128, 132, 138, 145, 155, 164, and 165 and a pharmaceutical carrier. 
     
     
         9 . An in vitro population of dendritic cells comprising the composition of  claim 4 . 
     
     
         10 . An antibody or antibody-like molecule that specifically binds to a phosphopeptide comprising the sequence selected from the group consisting of SEQ ID NOs: 70-171. 
     
     
         11 . The antibody or antibody-like molecule of  claim 10 , wherein the phosphopeptide comprises a sequence selected from the group consisting of SEQ ID NOs: 84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165. 
     
     
         12 . The antibody or antibody-like molecule of  claim 10 , wherein the antibody or antibody-like molecule is polyclonal, monoclonal, chimeric antibody, Fab fragments, or fragments produced by a Fab expression library or a T-cell receptor. 
     
     
         13 . A composition comprising the antibody or antibody-like molecule of  claim 10 , further comprising a pharmaceutically acceptable carrier. 
     
     
         14 . The composition of  claim 13 , further comprising an adjuvant. 
     
     
         15 . A method of inducing an immunogenic response comprising administering to a patient in need thereof a dose of the composition of  claim 4 . 
     
     
         16 . A method of treating or preventing cancer comprising administering to a patient in need thereof a dose of the composition of  claim 4 . 
     
     
         17 . A method of treating or preventing breast cancer comprising administering to a patient in need thereof a dose of a composition comprising an isolated phosphopeptide comprising a sequence selected from the group consisting of SEQ ID NOs:70-171 in combination with a pharmaceutically acceptable carrier. 
     
     
         18 . The method of  claim 17 , wherein the isolated phosphopeptide comprises a sequence selected from the group consisting of SEQ ID NO: 84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165. 
     
     
         19 . A method of treating or preventing breast cancer comprising administering to a patient in need thereof the population of the dendritic cells of  claim 9  in combination with a pharmaceutically acceptable carrier. 
     
     
         20 . A population of T-cells specific for a phosphopeptide of  claim 1 .