Inhbb epitope peptides and vaccines containing the same

Abstract

Peptide vaccines against cancer are described herein. In particular, the present invention describes epitope peptides derived from INHBB that elicit CTLs. The present invention also provides established CTLs that specifically recognize HLA-A02 positive target cells pulsed with the peptides. Antigen-presenting cells and exosomes that present any of the peptides, as well as methods for inducing antigen-presenting cells are also provided. The present invention further provides pharmaceutical compositions containing the INHBB polypeptides or polynucleotides encoding thereof, as well as exosomes and antigen-presenting cells as active ingredients. Furthermore, the present invention provides methods for the treatment and/or prophylaxis of cancers, and/or prevention of postoperative recurrence thereof, as well as methods for inducing CTLs, methods for inducing anti-tumor immunity, using the INHBB polypeptides, polynucleotides encoding the polypeptides, exosomes or antigen-presenting cells presenting the polypeptides, or the pharmaceutical agents of the present invention.

1 . An isolated peptide derived from SEQ ID NO: 16, wherein said peptide comprises an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NOs: 1 to 14; and   (b) SEQ ID NOs: 1 to 14, in which 1, 2, or several amino acids are substituted, inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility.   
     
     
         2 . The peptide as set forth in  claim 1 , wherein the peptide consists of less than 15 amino acid residues. 
     
     
         3 . The peptide as set forth in  claim 2 , wherein the peptide is a nonapeptide or a decapeptide. 
     
     
         4 . The peptide as set forth in  claims 1 , in which the peptide, comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 14, has one or both of the following characteristics:
 (a) the second amino acid from the N-terminus is selected from the group of leucine or methionine, and   (b) the C-terminal amino acid is selected from the group of valine or leucine.   
     
     
         5 . An isolated polynucleotide encoding one or more peptides as set forth in  claim 1 . 
     
     
         6 . A pharmaceutical agent comprising an active ingredient selected from the group consisting of:
 (a) one or more peptides as set forth in  claim 1 ;   (b) one or more polynucleotides encoding the peptide   (c) one or more antigen-presenting cells and/or exosomes, which present a complex formed between a HLA antigen and a peptide as set forth in  claim 1  on its surface,   (d) one or more CTLs induced against a peptide as set forth in  claim 1 ; and   (e) combinations thereof,   
       in combination with a pharmacologically acceptable carrier formulated for a purpose selected from the group consisting of:
 (i) treatment of cancer, 
 (ii) prophylaxis of cancer, 
 (iii) preventing postoperative recurrence of cancer, and 
 (iv) combinations thereof. 
 
     
     
         7 . The pharmaceutical agent as set forth in  claim 6 , formulated for administration to a subject whose HLA antigen is HLA-A02. 
     
     
         8 . The pharmaceutical agent of  claim 6 , wherein said cancer is selected from the group consisting of cholangio cellular carcinoma, esophageal cancer, non-small cell lung cancer (NSCLC), renal carcinoma, small cell lung cancer (SCLC) and soft tissue tumor. 
     
     
         9 . The pharmaceutical agent of  claim 6 , wherein said agent is formulated as a vaccine. 
     
     
         10 . A method for inducing an antigen-presenting cell with high CTL inducibility, wherein the method comprises the step selected from the group consisting of:
 (a) contacting an antigen-presenting cell with a peptide set forth in  claim 1 ; and   (b) introducing a polynucleotide encoding the peptide in an expressible form into an antigen-presenting cell.   
     
     
         11 . A method for inducing CTL, wherein the method comprises the step selected from the group consisting of:
 (a) contacting CD8-positive T cells with antigen-presenting cells and/or exosomes which present a complex formed between a HLA antigen and a peptide as set forth in  claim 1 ; and   (b) introducing a polynucleotide encoding a polypeptide which is capable of forming a TCR subunit recognizing a complex formed between a HLA antigen and a peptide as set forth in  claim 1  into a CD8-positive T cell.   
     
     
         12 . An isolated CTL which targets any of the peptides set forth in  claim 1 . 
     
     
         13 . An isolated CTL which is induced by a peptide as set forth in  claim 1 . 
     
     
         14 . The CTL as set forth in  claim 12 , which is capable of recognizing on a cell surface, a complex formed between a HLA antigen and a peptide which comprises an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NOs: 1 to 14: and   (b) SEQ ID NOs: 1 to 14, wherein 1, 2, or several amino acids are substituted, inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility.   
     
     
         15 . An isolated CTL which targets a peptide which comprises an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NOs: 1 to 14; and   (b) SEQ ID NOs: 1 to 14, wherein 1, 2, or several amino acids are substituted, inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility;   which is induced by the method as set forth in  claim 11 .   
     
     
         16 . An isolated antigen-presenting cell, which presents on its surface a complex formed between a HLA antigen and a peptide as set forth in  claim 1 . 
     
     
         17 . The antigen-presenting cell of  claim 16 , which is induced by the method of inducing an antigen-presenting cell with high CTL inducibility, wherein the method comprises the step selected from the group consisting of:
 (a) contacting an antigen-presenting cell with a peptide which comprises an amino acid sequence selected from the group consisting of:
 (i) SEQ ID NOs: 1 to 14; and 
 (ii) SEQ ID NOs: 1 to 14, wherein 1, 2, or several amino acids are substituted, inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility; and 
   (b) introducing a polynucleotide encoding the peptide in an expressible form into an antigen-presenting cell.   
     
     
         18 . The antigen-presenting cell as set forth in  claim 16 , wherein the HLA antigen is HLA-A02. 
     
     
         19 . An agent for inducing an immune response against a cancer in a subject, wherein said agent comprises an active ingredient selected from the group consisting of:
 (a) one or more peptides as set forth in  claim 1 ;   (b) one or more polynucleotides encoding the peptide in an expressible form;   (c) one or more antigen-presenting cells and/or exosomes, which antigen-presenting cells and exosomes present a complex formed between a HLA antigen and a peptide as set forth in  claim 1  on its surface;   (d) one or more CTLs induced against a peptide as set forth in  claim 1 ; and   (e) combinations thereof.   
     
     
         20 . A method of inducing an immune response against a cancer in a subject, said method comprising the step of administering to said subject an agent comprising an active ingredient selected from the group consisting of:
 (a) one or more peptides as set forth in  claim 1 ;   (b) one or more polynucleotides encoding the peptide in an expressible form;   (c) one or more antigen-presenting cells and/or exosomes, which antigen-presenting cells and exosomes present a complex formed between a HLA antigen and a peptide as set forth in  claim 1  on its surface;   (d) one or more CTLs induced against a peptide as set forth in  claim 1 ; and   (e) combinations thereof,   
       and a pharmaceutically acceptable carrier 
     
     
         21 . The method as set forth in  claim 20 , wherein said cancer is selected from the group consisting of cholangio cellular carcinoma, esophageal cancer, non-small cell lung cancer (NSCLC), renal carcinoma, small cell lung cancer (SCLC) and soft tissue tumor. 
     
     
         22 . The method as set forth in  claim 20 , wherein the subject has HLA A02. 
     
     
         23 . An agent for inducing CTL, wherein the agent comprises one or more peptides comprising an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NOs: 1 to 14; and   (b) SEQ ID NOs: 1 to 14, wherein 1, 2, or several amino acids are substituted., inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility;   a polynucleotide encoding the peptide, or an isolated antigen-presenting cell of  claim 16 .   
     
     
         24 . The CTL as set forth in  claim 13 , which is capable of recognizing on a cell surface, a complex formed between a HLA antigen and a peptide derived from SEQ ID NO: 16, wherein said peptide comprises an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NOs: 1 to 14; and   (b) SEQ ID NOs: 1 to 14, wherein 1, 2, or several amino acids are substituted, inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility.   
     
     
         25 . An isolated CTL which is induced by a peptide derived from SEQ ID NO: 16, wherein said peptide comprises an amino acid sequence selected from the group consisting of:
 (a) SEQ ID NOs: 1 to 14; and   (b) SEQ ID NOs: 1 to 14, wherein 1, 2, or several amino acids are substituted, inserted, deleted and/or added, and has cytotoxic T lymphocyte (CTL) inducibility;   which is induced by the method as set forth in  claim 11 .   
     
     
         26 . The antigen-presenting cell as set forth in  claim 17 , wherein the HLA antigen is HLA-A02.