Ssx-2 peptides presented by hla class ii molecules

Abstract

The invention describes HLA class II binding peptides encoded by the SSX-2 tumor associated gene, as well as nucleic acids encoding such peptides and antibodies relating to the peptides. The peptides stimulate the activity and proliferation of CD4 + T lymphocytes. Methods and products also are provided for diagnosing and treating conditions characterized by expression of the SSX-2 gene.

1 . A method for inducing an immune response in a subject having a cancer characterized by expression of SSX-2 comprising:
 administering to the subject an amount of a SSX-2 HLA class II-binding peptide effective to induce an immune response,   wherein the SSX-2 HLA class II-binding peptide comprises an amino acid sequence set forth as SEQ ID NO:54, wherein the HLA class II-binding peptide does not include a full length SSX-2 protein.   
     
     
         2 . The method of  claim 1 , wherein the SSX-2 HLA class II-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:52 and SEQ ID NO:55. 
     
     
         3 . The method of  claim 2 , wherein the SSX-2 HLA class II-binding peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:52, SEQ ID NO:54 and SEQ ID NO:55. 
     
     
         4 . The method of  claim 1 , wherein the SSX-2 HLA class II binding peptide comprises an endosomal targeting signal. 
     
     
         5 . The method of  claim 4 , wherein the endosomal targeting signal comprises an endosomal targeting portion of human invariant chain Ii. 
     
     
         6 . The method of  claim 1 , wherein the isolated peptide is non-hydrolyzable. 
     
     
         7 . The method of  claim 6 , wherein the isolated peptide is selected from the group consisting of peptides comprising D-amino acids, peptides comprising a -psi[CH 2 NH]-reduced amide peptide bond, peptides comprising a -psi[COCH 2 ]-ketomethylene peptide bond, peptides comprising a -psi[CH(CN)NH]-(cyanomethylene)amino peptide bond, peptides comprising a -psi[CH 2 CH(OH)]-hydroxyethylene peptide bond, peptides comprising a -psi[CH 2 O]-peptide bond, and peptides comprising a -psi[CH 2 S]-thiomethylene peptide bond. 
     
     
         8 . A method for inducing an immune response in a subject having a cancer characterized by expression of SSX-2 comprising:
 administering to the subject an amount of a HLA class I-binding peptide and an amount of a SSX-2 HLA class II-binding peptide effective to induce an immune response,   wherein the SSX-2 HLA class II-binding peptide comprises an amino acid sequence set forth as SEQ ID NO:54, wherein the HLA class II-binding peptide does not include a full length SSX-2 protein.   
     
     
         9 . The method of  claim 8 , wherein the SSX-2 HLA class II-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:52, SEQ ID NO:53 and SEQ ID NO:55. 
     
     
         10 . The method of  claim 9 , wherein the SSX-2 HLA class II-binding peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54 and SEQ ID NO:55. 
     
     
         11 . The method of  claim 8 , wherein the HLA class I-binding peptide and the SSX-2 HLA class II-binding peptide are combined as a polytope polypeptide. 
     
     
         12 . The method of  claim 8 , wherein the HLA class I-binding peptide is a SSX-2 HLA class I-binding peptide. 
     
     
         13 . The method of  claim 8 , wherein the SSX-2 HLA class II binding peptide comprises an endosomal targeting signal. 
     
     
         14 . The method of  claim 13 , wherein the endosomal targeting signal comprises an endosomal targeting portion of human invariant chain Ii. 
     
     
         15 . The method of  claim 8 , wherein the isolated peptide is non-hydrolyzable. 
     
     
         16 . The method of  claim 15 , wherein the isolated peptide is selected from the group consisting of peptides comprising D-amino acids, peptides comprising a -psi[CH 2 NH]-reduced amide peptide bond, peptides comprising a -psi[COCH 2 ]-ketomethylene peptide bond, peptides comprising a -psi[CH(CN)NH]-(cyanomethylene)amino peptide bond, peptides comprising a -psi[CH 2 CH(OH)]-hydroxyethylene peptide bond, peptides comprising a -psi[CH 2 O]-peptide bond, and peptides comprising a -psi[CH 2 S]-thiomethylene peptide bond. 
     
     
         17 . A method for inducing an immune response in a subject having a cancer characterized by expression of SSX-2 comprising:
 administering to the subject an amount of autologous CD4+ T lymphocytes sufficient to induce an immune response, wherein the CD4+ T lymphocytes are specific for complexes of an HLA class II molecule and a SSX-2 HLA class II-binding peptide,   wherein the SSX-2 HLA class II-binding peptide comprises an amino acid sequence set forth as SEQ ID NO:54, wherein the HLA class II-binding peptide does not include a full length SSX-2 protein.   
     
     
         18 . The method of  claim 17 , wherein the SSX-2 HLA class II-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:52 and SEQ ID NO:55. 
     
     
         19 . The method of  claim 18 , wherein the SSX-2 HLA class II-binding peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:52, SEQ ID NO:54 and SEQ ID NO:55.