Tmem22 peptides and vaccines including the same

Abstract

Isolated peptides composed of the amino acid sequence of SEQ ID NO: 33 or fragments thereof that bind to HLA antigens and have cytotoxic T lymphocyte (CTL) inducibility and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines are described herein. The present invention further provides peptides that include one, two, or several amino acid insertions, substitutions or additions to the aforementioned peptides or fragments, but yet retain the requisite cytotoxic T cell inducibility. Further provided are nucleic acids encoding any of these aforementioned peptides as well as pharmaceutical agents, substances and compositions including any of the aforementioned peptides or nucleic acids. The peptides, nucleic acids, pharmaceutical agents, substances and compositions of this invention find particular utility in the treatment of cancers and tumors.

1 . An isolated peptide of (a), (b) or (c) below:
 (a) a peptide consisting of the amino acid sequence of SEQ ID NO: 92 or an immunologically active fragment thereof;   (b) a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 10, 12, 16, 18, 19, 22, 28, 31, 35, 38, 41, 48, 61, 62, 65, 67, 70, 77 and 83;   (c) a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 10, 12, 16, 18, 19, 22, 28, 31, 35, 38, 41, 48, 61, 62, 65, 67, 70, 77 and 83, in which 1, 2 or several amino acid(s) are inserted, substituted, deleted or added,   wherein the peptide has cytotoxic T lymphocyte (CTL) inducibility.   
     
     
         2 . The isolated peptide of  claim 1 , wherein, in the context of HLA-A24, the peptide has one or both of the following characteristics:
 (a) the second amino acid from the N-terminus is selected from the group of phenylalanine, tyrosine, methionine and tryptophan; and   (b) the C-terminal amino acid is selected from the group of phenylalanine, leucine, isoleucine, tryptophan and methionine.   
     
     
         3 . The isolated peptide of  claim 1 , wherein, in the context of HLA-A2, has one or both of the following characteristics:
 (a) the second amino acid from the N-terminus is selected from the group consisting of leucine and methionine; and   (b) the C-terminal amino acid is selected from the group consisting of valine and leucine.   
     
     
         4 . The isolated peptide of  claim 1 , wherein said peptide is a nonapeptide or decapeptide. 
     
     
         5 . An isolated polynucleotide encoding a peptide of  claim 1 . 
     
     
         6 . An agent for inducing CTL, wherein the agent comprises one or more peptide(s) of  claim 1 , or one or more polynucleotide(s) of encoding said peptide(s). 
     
     
         7 . A pharmaceutical agent for the treatment and/or prophylaxis of cancer, and/or the prevention of a postoperative recurrence thereof, wherein the agent comprises one or more peptide(s) of  claim 1 , or one or more polynucleotide(s) of encoding said peptide(s). 
     
     
         8 . The pharmaceutical agent of  claim 7 , wherein said agent is formulated for the administration to a subject whose HLA antigen is HLA-A24 or HLA-A2. 
     
     
         9 . A method for inducing an antigen-presenting cell (APC) with CTL inducibility, wherein the method comprises one of the following steps:
 (a) contacting an APC with a peptide of  claim 1  in vitro, ex vivo or in vivo; and   (b) introducing a polynucleotide encoding a peptide of  claim 1  into an APC.   
     
     
         10 . A method for inducing CTL by any of the methods comprising at least one of the following steps:
 (a) co-culturing CD8-positive T cells with APCs, which presents on its surface a complex of an HLA antigen and a peptide of  claim 1 ;   (b) co-culturing CD8-positive T cells with exosomes, which presents on its surface a complex of an HLA antigen and a peptide of  claim 1 ; and   (c) introducing a gene that comprises a polynucleotide encoding a T cell receptor (TCR) subunit polypeptide binding to a peptide of  claim 1  into a T cell.   
     
     
         11 . An isolated APC that presents on its surface a complex of an HLA antigen and a peptide of  claim 1 . 
     
     
         12 . The APC of  claim 11 , which is induced by a method for inducing an antigen-presenting cell (APC) with CTL inducibility, wherein the method comprises one of the following steps:
 (a) contacting an APC with said peptide in vitro, ex vivo or in vivo; and   (b) introducing a polynucleotide encoding said peptide into an APC.   
     
     
         13 . An isolated CTL that targets a peptide of  claim 1 . 
     
     
         14 . The CTL of  claim 13 , which is induced by a method for inducing CTL by any of the methods comprising at least one of the following steps:
 (a) co-culturing CD8-positive T cells with APCs, which presents on its surface a complex of an HLA antigen and said peptide;   (b) co-culturing CD8-positive T cells with exosomes, which presents on its surface a complex of an HLA antigen and said peptide; and   (c) introducing a gene that comprises a polynucleotide encoding a T cell receptor (TCR) subunit polypeptide binding to said peptide into a T cell.   
     
     
         15 . A method of inducing immune response against cancer in a subject comprising administering to the subject an agent comprising a peptide of  claim 1 , an immunologically active fragment thereof, or a polynucleotide encoding the peptide or the fragment. 
     
     
         16 . A vector comprising a nucleotide sequence encoding the peptide as set forth in  claim 1 . 
     
     
         17 . A host cell transformed or transfected with an expression vector according to  claim 16 . 
     
     
         18 . The isolated peptide of  claim 1 , which consist of the amino acid sequence selected from the group of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 10, 12, 16, 18, 19, 22, 28, 31, 35, 38, 41, 48, 61, 62, 65, 67, 70, 77 and 83.