Tumor antigen peptide
The purpose of the present invention is to provide: a detection agent for specifically detecting a cancer stem cell; a tumor antigen peptide specifically presented by cancer stem cells; a medicinal composition useful in preventing and/or treating cancer, said medicinal composition comprising the aforementioned tumor antigen peptide as an active ingredient; a method for screening the tumor antigen peptide; etc. To achieve the above-mentioned purpose, provided are: peptides represented by Y O -X O -Z O ; a polyepitope peptide consisting of a plurality of epitope peptides connected together, said polyepitope peptide containing at least one of the above-mentioned peptides as one of the epitope peptides; a polynucleotide encoding the aforementioned peptides and/or polyepitope peptide; a medicinal composition comprising the same as an active ingredient; a prophylactic and/or therapeutic agent for cancer characterized by inducing CTL; etc.
1. An antigen peptide represented by Y 0 -X 0 -Z 0 , wherein
X 0 is any of (1) to (2) below:
(1) SEQ ID NO: 3 in which the second amino acid from the N terminal is replaced by leucine, isoleucine or methionine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine;
or
(2) SEQ ID NO: 3 in which the second amino acid from the N terminal is replaced by phenylalanine, methionine or tryptophan, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and,
Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids.
2. The antigen peptide according to claim 1 , wherein X 0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, leucine or isoleucine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine; and
Y 0 and Z 0 are not present.
3. The antigen peptide according to claim 1 , wherein X 0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and
Y 0 and Z 0 are not present.
4. An antigen peptide represented by Y 0 -X 0 -Z 0 wherein X 0 consists of an amino acid sequence represented by SEQ ID NO: 3, either one of Y 0 or Z 0 is one amino acid, and the other is not present, provided that Y 0 is not arginine and Z 0 is not isoleucine.
5. A polyepitope peptide which comprises a plurality of epitope peptides linked together, wherein the polyepitope peptide comprises at least one antigen peptide according to claim 1 or any of a peptide represented by Y 0 -X 0 -Z 0 , wherein X 0 is SEQ ID NO. 3, and Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids as the epitope peptide.
6. A polynucleotide encoding at least one of the antigen peptide according to claim 1 or claim 4 .
7. An expression vector comprising the polynucleotide according to claim 6 .
8. A gene transfer composition comprising the expression vector according to claim 7 .
9. A pharmaceutical composition comprising as an active ingredient any of (a) to (c) below:
(a) the antigen peptide according to claim 1 or claim 4 ,
(b) a polynucleotide encoding the peptide according to claim 1 or claim 4 ,
(c) an expression vector comprising the polynucleotide encoding the peptide according to claim 1 or claim 4 .
10. The pharmaceutical composition according to claim 9 , wherein the active ingredient is (a) the antigen peptide.
11. The pharmaceutical composition according to claim 9 , further comprising an adjuvant.
12. The pharmaceutical composition according to claim 9 , wherein the pharmaceutical composition is an agent against recurrence and metastasis of cancer and/or therapeutic agent for cancer.
13. The pharmaceutical composition according to claim 9 , wherein the pharmaceutical composition is a vaccine for the prevention of recurrence and metastasis and/or treatment of a cancer.
14. An agent for inducing cytotoxic T cells, the agent comprising as an active ingredient any of (a) to (c) below:
(a) the antigen peptide according to claim 1 or claim 4 ,
(b) a polynucleotide encoding the peptide according to claim 1 or claim 4 ,
(c) an expression vector comprising the polynucleotide encoding the peptide according to claim 1 or claim 4 .
15. A method for producing an antigen-presenting cell, the method comprising contacting in vitro a cell having an antigen-presenting ability with
(A) the antigen peptide according to claim 1 or any of a peptide represented by Y 0 -X 0 -Z 0 , wherein X 0 is SEQ ID NO. 3, and Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids, or
(B) a polynucleotide encoding at least one of the peptide of (A).
16. A method for inducing a cytotoxic T cell, the method comprising contacting in vitro a peripheral blood lymphocyte with
(A) the antigen peptide according to claim 1 or any of a peptide represented by Y 0 -X 0 -Z 0 , wherein X 0 is SEQ ID NO. 3, and Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids, or
(B) a polynucleotide encoding at least one of the antigen peptide of (A).
17. An HLA multimer comprising an HLA and the antigen peptide according to claim 1 or claim 4 .
18. A diagnostic agent comprising the HLA multimer according to claim 17 .
19. The antigen peptide according to claim 1 , wherein X 0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, leucine or isoleucine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine, either one of Y 0 or Z 0 is one amino acid, and the other is not present.
20. The antigen peptide according to claim 1 , wherein X 0 consists of an amino acid sequence represented by SEQ ID NO: 3, in which the second amino acid from the N terminal is replaced by methionine, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine, either one of Y 0 or Z 0 is one amino acid, and the other is not present.
21. A method for treating a subject having cancer comprising administering to the subject an effective amount of the peptide according to claim 1 or claim 4 .
22. A method for treating a subject having cancer comprising administering to the subject an effective amount of the polynucleotide according to claim 6 .
23. A method for treating a subject having cancer comprising administering to the subject an effective amount of CTLs induced by the method according to claim 16 .
24. A method for treating a subject having cancer comprising administering to the subject an effective amount of antigen presenting cells produced by the method according to claim 15 .
25. A pharmaceutical composition comprising as an active ingredient a peptide represented by Y 0 -X 0 -Z 0 , wherein X 0 is SEQ ID NO. 3, and Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids; and an adjuvant.
26. A method for treating a subject having cancer comprising administering to the subject an effective amount of a peptide represented by Y 0 -X 0 -Z 0 , wherein X 0 is SEQ ID NO. 3 and Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids.
27. A method for treating a subject having cancer comprising administering to the subject an effective amount of a polynucleotide encoding a peptide represented by Y 0 -X 0 -Z 0 , wherein X 0 is SEQ ID NO. 3 and Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids.
28. An antigen peptide represented by Y 0 -X 0 -Z 0 , wherein
X 0 is any of (1) to (2) below:
(1) SEQ ID NO: 28 in which the second amino acid from the N terminal is replaced by leucine or methionine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine;
or
(2) SEQ ID NO: 28 in which the second amino acid from the N terminal is replaced by tyrosine, phenylalanine, methionine or tryptophan, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and,
Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids.
29. An antigen peptide represented by Y 0 -X 0 -Z 0 , wherein
X 0 is any of (1) to (2) below:
(1) SEQ ID NO: 4 in which the second amino acid from the N terminal is replaced by isoleucine or methionine, and/or the amino acid at the C terminal is replaced by leucine or isoleucine;
or
(2) SEQ ID NO: 4 in which the second amino acid from the N terminal is replaced by tyrosine, phenylalanine, methionine or tryptophan, and/or the amino acid at the C terminal is replaced by leucine, isoleucine or phenylalanine; and,
Y 0 and Z 0 are mutually independently a peptide consisting of 0 to 5 amino acids.