Urlc10-derived peptide and vaccine containing same

Abstract

The present invention provides URLC10-derived epitope peptides having the ability to induce cytotoxic T cells. The present invention further provides polynucleotides encoding the peptides, antigen-presenting cells presenting the peptides, and cytotoxic T cells targeting the peptides, as well as methods of inducing the antigen-presenting cells or CTLs. The present invention also provides compositions and pharmaceutical compositions containing them as an active ingredient. Further, the present invention provides methods of treating and/or preventing cancer, and/or preventing postoperative recurrence thereof, using the peptides, polynucleotides, antigen-presenting cells, cytotoxic T cells or pharmaceutical compositions of the present invention. Methods of inducing an immune response against cancer are also provided.

1 . An isolated peptide of less than 15 amino acids having cytotoxic T cell (CTL)-inducing ability, which comprises the amino acid sequence selected from the group of:
 (a) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 9, 5, 6, 3, 12, 22, 14, 16, 18, 15, 27, 17, 30 and 31; and   (b) the amino acid sequence in which one, two or several amino acids are substituted, deleted, inserted and/or added to the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 9, 5, 6, 3, 12, 22, 14, 16, 18, 15, 27, 17, 30 and 31.   
     
     
         2 . The peptide of  claim 1 , which is selected from the group consisting of (i) to (ii) below:
 (i) a peptide comprising the amino acid sequence in which one or more substitution(s) selected from the group consisting of (a) to (d) below is introduced into the amino acid sequence selected from the group consisting of SEQ ID NOs: 1 and 9:
 (a) the second amino acid from the N-terminus is substituted with an amino acid selected from the group consisting of threonine, valine, isoleucine, leucine, phenylalanine and tyrosine; 
 (b) the third amino acid from the N-terminus is substituted with an amino acid selected from the group consisting of leucine, phenylalanine, tyrosine, isoleucine and alanine; 
 (c) the seventh amino acid from the N-terminus is substituted with an amino acid selected from the group consisting of leucine, isoleucine, tyrosine, valine and phenylalanine; and 
 (d) the C-terminal amino acid is substituted with an amino acid selected from the group consisting of lysine and arginine; 
   (ii) a peptide comprising the amino acid sequence in which one or more substitution(s) selected from the group consisting of (a) to (b) below is introduced into the amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 1, 6, 3, 12, 22, 14, 16, 18, 15, 27, 17, 30 and 31:
 (a) the second amino acid from the N-terminus is substituted with an amino acid selected from the group consisting of leucine, methionine, valine, alanine, isoleucine, serine and threonine; and 
 (b) the C-terminal amino acid is substituted with an amino acid selected from the group consisting of arginine, lysine, tyrosine and phenylalanine. 
   
     
     
         3 . The peptide of  claim 1 , which consists of the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 9, 5, 6, 3, 12, 22, 14, 16, 18, 15, 27, 17, 30 and 31. 
     
     
         4 . An isolated polynucleotide, which encodes the peptide of  claim 1 . 
     
     
         5 . A composition comprising a pharmaceutically acceptable carrier and at least one ingredient selected from the group consisting of (a) to (e) below:
 (a) one or more types of peptides of  claim 1 ;   (b) one or more types of polynucleotides encoding the peptide(s) of  claim 1  in an expressible form;   (c) an antigen-presenting cell (APC) that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen;   (d) an exosome that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen; and   (e) a CTL that targets the peptide of  claim 1 .   
     
     
         6 . A method of inducing an APC(s) having CTL-inducing ability, which comprises a step selected from the group consisting of:
 (a) contacting an APC(s) with the peptide of  claim 1  in vitro, ex vivo or in vivo; and   (b) introducing a polynucleotide encoding the peptide of  claim 1  into an APC(s).   
     
     
         7 . A method of inducing a CTL(s), which comprises a step selected from the group consisting of:
 (a) co-culturing a CD8-positive T cell(s) with an APC(s) that presents on its surface a complex of an HLA antigen and the peptide of  claim 1 ;   (b) co-culturing a CD8-positive T cell(s) with an exosome(s) that presents on its surface a complex of an HLA antigen and the peptide of  claim 1 ; and   (c) introducing into a CD8-positive T cell(s) a polynucleotide encoding each subunit of a T cell receptor (TCR) capable of binding to the peptide of  claim 1  presented by an HLA antigen on a cell surface.   
     
     
         8 . An isolated APC that presents on its surface a complex of an HLA antigen and the peptide of  claim 1 . 
     
     
         9 . An isolated APC which is induced by a method comprising a step selected from the group consisting of:
 (a) contacting an APC(s) with the peptide of  claim 1  in vitro, ex vivo or in vivo; and   (b) introducing a polynucleotide encoding the peptide of  claim 1  into an APC(s).   
     
     
         10 . An isolated CTL that targets the peptide of  claim 1 . 
     
     
         11 . An isolated CTL which is induced by a method comprising a step selected from the group consisting of:
 (a) co-culturing a CD8-positive T cell(s) with an APC(s) that presents on its surface a complex of an HLA antigen and the peptide of  claim 1 ;   (b) co-culturing a CD8-positive T cell(s) with an exosome(s) that presents on its surface a complex of an HLA antigen and the peptide of  claim 1 ; and   (c) introducing into a CD8-positive T cell(s) a polynucleotide encoding each subunit of a T cell receptor (TCR) capable of binding to the peptide of  claim 1  presented by an HLA antigen on a cell surface.   
     
     
         12 . A method of inducing an immune response against cancer, which comprises administering to a subject at least one ingredient selected from the group consisting of (a) to (e) below:
 (a) one or more types of peptides of  claim 1 ;   (b) one or more types of polynucleotides encoding the peptide(s) of  claim 1  in an expressible form;   (c) an antigen-presenting cell (APC) that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen;   (d) an exosome that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen; and   (e) a CTL that targets the peptide of  claim 1 .   
     
     
         13 . A method of treating and/or preventing cancer, and/or preventing postoperative recurrence thereof, which comprises administering to a subject at least one ingredient selected from the group consisting of (a) to (e) below:
 (a) one or more types of peptides of  claim 1 ;   (b) one or more types of polynucleotides encoding the peptide(s) of  claim 1  in an expressible form;   (c) an antigen-presenting cell (APC) that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen;   (d) an exosome that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen; and   (e) a CTL that targets the peptide of  claim 1 .   
     
     
         14 . An antibody that binds to the peptide of  claim 1 . 
     
     
         15 . A method of screening for a peptide having CTL-inducing ability, which comprises the steps of:
 (a) generating candidate sequences consisting of an amino acid sequence in which one, two or several amino acid residues are substituted, deleted, inserted and/or added in an original amino acid sequence consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 9, 5, 6, 3, 12, 22, 14, 16, 18, 15, 27, 17, 30 and 31;   (b) selecting from among the candidate sequences generated in (a), a candidate sequence that does not have significant homology (sequence identity) with any known human gene product other than URLC10;   (c) contacting an APC(s) with a peptide consisting of the candidate sequence selected in (b);   (d) contacting the APC(s) of (c) with a CD8-positive T cell(s); and   (e) selecting a peptide having an equal to or higher CTL-inducing ability than that of a peptide consisting of the original amino acid sequence.   
     
     
         16 . An emulsion comprising one or more types of peptides of  claim 1 , a water-soluble carrier and an oil adjuvant. 
     
     
         17 . A kit comprising a container that houses a composition comprising a pharmaceutically acceptable carrier and at least one ingredient selected from the group consisting of (a) to (e) below:
 (a) one or more types of peptides of  claim 1 ;   (b) one or more types of polynucleotides encoding the peptide(s) of  claim 1  in an expressible form;   (c) an antigen-presenting cell (APC) that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen;   (d) an exosome that presents on its cell surface a complex of the peptide of  claim 1  and an HLA antigen; and   (e) a CTL that targets the peptide of  claim 1 ,   
       and a container that houses an adjuvant.