Melanoma associated peptide analogues and vaccines against melanoma

Abstract

The present invention is concerned with cancer treatment and diagnosis, especially with melanoma associated peptide analogues with improved immunogenicity, epitopes thereof, vaccines against melanoma, tumor infiltrating T lymphocytes recognizing the antigen and diagnostics for the detection of melanoma and for the monitoring of vaccination. The peptides according to the invention can be exploited to elicit native epitope-reactive Cm. Usage of the peptides with improved immunogenicity may contribute to the development of CTL-epitope based vaccines in viral disease and cancer.

What is claimed is:  
     
         1 . A peptide comprising: 
 at least part of the amino acid sequence of SEQ ID NO:9 wherein an original amino acid at position 2 thereof is substituted with valine and    wherein said peptide is immunogenic with lymphocytes directed against metastatic melanomas.    
     
     
         2 . The peptide of  claim 1 , wherein the original amino acid at position 8, glutamine, is substituted by replacement amino acid, alanine.  
     
     
         3 . The peptide of  claim 2 , wherein the original amino acid at position 2, threonine, is substituted by a replacement amino acid selected from the group consisting of isoleucine, leucine, and valine.  
     
     
         4 . The peptide of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 1.  
     
     
         5 . A nucleic acid which comprises a nucleotide sequence encoding the peptide of  claim 1 .  
     
     
         6 . A vaccine comprising the peptide of  claim 1  or a nucleotide sequence encoding said peptide.  
     
     
         7 . The vaccine of  claim 6 , further comprising a pharmaceutically acceptable carrier or diluent.  
     
     
         8 . The vaccine of  claim 6 , wherein an antigen presenting cell has been preloaded with the peptide.  
     
     
         9 . A vaccine which comprises a T cell receptor against the peptide of  claim 1  or cells expressing said T cell receptor.  
     
     
         10 . The vaccine of  claim 6 , characterized in that it also comprises one or more compounds selected from the group consisting of an adjuvant, one or more cytokines, antibodies directed against CD2, CD3, CD27, CD28 or other T cell surface antigens and helper epitopes to stimulate CD4+ or CD8+ T cells.  
     
     
         11 . The vaccine of  claim 9 , characterized in that it also comprises one or more compounds selected from the group consisting of an adjuvant, one or more cytokines, antibodies directed against CD2, CD3, CD27, CD28 or other T cell surface antigens and helper epitopes to stimulate CD4+ or CD8+ T cells  
     
     
         12 . Tumor infiltrating lymphocytes which bind to the peptide of  claim 1 .  
     
     
         13 . A vaccine comprising the tumor infiltrating lymphocytes of  claim 13 .  
     
     
         14 . An antibody directed against the peptide of  claim 1 .  
     
     
         15 . A composition comprising the antibody of  claim 14 .  
     
     
         16 . A method for monitoring progress of immunotherapy in a subject, the method comprising: 
 detecting the presence of antibodies directed to the peptide of  claim 1  in the serum of the subject as indicative of the progress of immunotherapy.