DEPDC1-derived peptide and vaccine containing same
The present invention provides DEPDC1-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 of SEQ ID NO: 1 into which one or two substitution(s) selected from the group consisting of (a) to (d) below is introduced:
(a) the second amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with an amino acid selected from the group consisting of leucine, phenyalanine, tyrosine, isoleucine, and alanine;
(c) the seventh amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with arginine.
2. A composition comprising a pharmaceutically acceptable carrier and one or more types of peptides selected from the group consisting of (i) to (ii) below:
(i) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1; and
(ii) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1 into which one or two substitution(s) selected from the group consisting of (a) to (d) below is introduced:
(a) the second amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with arginine;
in combination with an adjuvant in an amount to enhance an immune response.
3. The composition of claim 2 , which is for inducing a CTL(s).
4. The composition of claim 2 , which is a pharmaceutical composition.
5. The composition of claim 4 , which is for cancer treatment.
6. The composition of claim 4 , which is for inducing an immune response against cancer.
7. The composition of claim 5 , wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, cervical cancer, cholangiocellular cancer, chronic myeloid leukemia (CML), colon cancer, gastric cancer, non-small-cell lung cancer (NSCLC), lymphoma, osteosarcoma, prostate cancer, small-cell lung cancer (SCLC), and soft tissue tumor.
8. The composition of claim 2 , which is formulated for administration to a subject positive for HLA-A11.
9. A method of inducing an APC(s) having CTL-inducing ability, which comprises contacting an APC(s) with a peptide in vitro, ex vivo, or in vivo, wherein the peptide is selected from the group consisting of (i) to (ii) below:
(i) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1; and
(ii) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1 into which one or two substitution(s) selected from the group consisting of (a) to (d) below is introduced:
(a) the second amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with an amino acid selected from the group consisting of leucine, isoleucine, tyrosine, valine, and phenyalanine; and
(d) the C-terminal amino acid in the amino acid sequence of SEQ ID NO: 1 is substituted with arginine.
10. A method of inducing a CTL(s), which comprises co-culturing a CD8-positive T cell(s) with an APC(s) that presents on its surface a complex of an HLA antigen and a peptide, wherein the peptide is selected from the group consisting of (i) to (ii) below:
(i) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1; and
(ii) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1 into which one or two substitution(s) selected from the group consisting of (a) to (d) below is introduced:
(a) the second amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 is substituted with an amino acid selected from the group consisting of threonine, valine, isoleucine, leucine, phenyalanine, and tyrosine;
(b) the third amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with arginine.
11. A method of inducing an immune response against cancer, which comprises administering to a subject the composition of claim 2 .
12. A method of treating cancer, which comprises administering to a subject the composition of claim 2 .
13. An emulsion comprising one or more types of peptides selected from the group consisting of (i) to (ii) below:
(i) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1; and
(ii) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1 into which one or two substitution(s) selected from the group consisting of (a) to (d) below is introduced:
(a) the second amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with arginine;
a water-soluble carrier; and
an oil adjuvant in an amount to enhance an immune response.
14. A kit comprising a container that houses a composition comprising a pharmaceutically acceptable carrier and one or more types of peptides selected from the group consisting of (i) to (ii) below:
(i) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1; and
(ii) a peptide of less than 15 amino acids having CTL-inducing ability, which comprises the amino acid sequence of SEQ ID NO: 1 into which one or two substitution(s) selected from the group consisting of (a) to (d) below is introduced:
(a) the second amino acid from the N terminus in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 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 in the amino acid sequence of SEQ ID NO: 1 is substituted with arginine;
and a container that houses an adjuvant in an amount effective to enhance an immune response.
15. The composition of claim 2 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.
16. The emulsion of claim 13 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.
17. The kit of claim 14 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 1.