FOXM1-derived peptide, and vaccine including same
The present invention provides FOXM1-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, wherein the peptide has cytotoxic T cell (CTL)-inducing ability and comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, into which one, two or three amino acid substitutions are introduced; wherein the peptide is selected from the group consisting of:
(i) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45 and 46, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(a) substitution of the first amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid;
(b) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of phenylalanine, tyrosine, alanine, isoleucine, leucine and valine; and
(c) substitution of the C-terminal amino acid with an amino acid selected from the group consisting of arginine and lysine; and
(ii) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(a) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of threonine and serine;
(b) substitution of the third amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid; and
(c) substitution of the C-terminal amino acid with tyrosine.
2. An isolated polynucleotide, which encodes the peptide of claim 1 .
3. A composition comprising a pharmaceutically acceptable carrier, an adjuvant in an amount effective for enhancing cellular immunity, and at least one ingredient selected from the group consisting of:
(a) an isolated peptide of less than 15 amino acids, wherein the peptide has cytotoxic T cell (CTL)-inducing ability and comprises the amino acid sequence selected from the group consisting of:
(i) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61; and
(ii) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 20, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, into which one, two or three amino acid substitutions are introduced; wherein the peptide is selected from the group consisting of:
(1) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45 and 46, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the first amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid;
(B) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of phenylalanine, tyrosine, alanine, isoleucine, leucine and valine; and
(C) substitution of the C-terminal amino acid with an amino acid selected from the group consisting of arginine and lysine; and
(2) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of threonine and serine;
(B) substitution of the third amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid; and
(C) substitution of the C-terminal amino acid with tyrosine;
(b) a polynucleotide encoding the peptide of (a) in an expressible form;
(c) an antigen-presenting cell (APC) that presents on its cell surface a complex of the peptide of (a) and an HLA antigen; and
(d) an exosome that presents on its surface a complex of the peptide of (a) and an HLA antigen.
4. A method of inducing a CTL(s), the 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 an isolated peptide of of less than 15 amino acids, wherein the peptide has cytotoxic T cell (CTL)-inducing ability and comprises the amino acid sequence selected from the group consisting of:
(i) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61; and
(ii) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, into which one, two or three amino acid substitutions are introduced; wherein the peptide is selected from the group consisting of:
(1) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45 and 46, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the first amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid;
(B) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of phenylalanine, tyrosine, alanine, isoleucine, leucine and valine; and
(C) substitution of the C-terminal amino acid with an amino acid selected from the group consisting of arginine and lysine; and
(2) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of threonine and serine;
(B) substitution of the third amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid; and
(C) substitution of the C-terminal amino acid with tyrosine; and
(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 (a).
5. A method of inducing an immune response against cancer, the method comprising administering to a subject at least one ingredient selected from the group consisting of:
(a) an isolated peptide of less than 15 amino acids, wherein the peptide has cytotoxic T cell (CTL)-inducing ability and comprises the amino acid sequence selected from the consisting of:
(i) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61; and
(ii) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, into which one, two or three amino acid substitutions are introduced; wherein the peptide is selected from the group consisting of:
(1) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45 and 46, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the first amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid;
(B) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of phenylalanine, tyrosine, alanine, isoleucine, leucine and valine; and
(C) substitution of the C-terminal amino acid with an amino acid selected from the group consisting of arginine and lysine; and
(2) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of threonine and serine;
(B) substitution of the third amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid; and
(C) substitution of the C-terminal amino acid with tyrosine;
(b) a polynucleotide encoding the peptide of (a) in an expressible form;
(c) an APC that presents on its cell surface a complex of the peptide of (a) and an HLA antigen; and
(d) an exosome that presents on its surface a complex of the peptide of (a) and an HLA antigen.
6. A method of treating cancer, the method comprising administering to a subject at least one ingredient selected from the group consisting of:
(a) an isolated peptide of less than 15 amino acids, wherein the peptide has cytotoxic T cell (CTL)-inducing ability and comprises the amino acid sequence selected from the group below:
(i) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61; and
(ii) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, into which one, two or three amino acid substitutions are introduced; wherein the peptide is selected from the group consisting of:
(1) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45 and 46, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the first amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid;
(B) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of phenylalanine, tyrosine, alanine, isoleucine, leucine and valine; and
(C) substitution of the C-terminal amino acid with an amino acid selected from the group consisting of arginine and lysine; and
(2) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the second amino acid from the N terminus with an amino acid selected from the group consisting of threonine and serine;
(B) substitution of the third amino acid from the N terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid; and
(C) substitution of the C-terminal amino acid with tyrosine;
(b) a polynucleotide encoding the peptide of (a) in an expressible form;
(c) an APC that presents on its cell surface a complex of the peptide of (a) and an HLA antigen; and
(d) an exosome that presents on its surface a complex of the peptide of (a) and an HLA antigen.
7. An emulsion comprising a water soluble carrier, an oil adjuvant in an amount effective for enhancing cellular immunity, and an isolated peptide of less than 15 amino acids having cytotoxic T cell (CTL)-inducing ability wherein said peptide comprises an amino acid sequence selected from the group consisting of:
(i) the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61; and
(ii) the amino acid sequence s into which elected from the group consisting of SEQ ID NOs: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45, 46, 48, 49, 50, 52, 53, 55, 57, 58, 59, 60 and 61 into which one, two or three amino acids are introduced, wherein the peptide is selected from the group consisting of:
(1) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 1, 2, 3, 6, 7, 11, 12, 17, 18, 22, 24, 26, 32, 33, 36, 39, 41, 42, 45 and 46, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the first amino acid from the N-terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid;
(B) substitution of the second amino acid from the N-terminus with an amino acid selected from the group consisting of phenylalanine, tyrosine, alanine, isoleucine, leucine and valine; and
(C) substitution of the C-terminal amino acid with an amino acid selected from the group consisting of arginine and lysine; and
(2) a peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 48, 39, 50, 52, 53, 55, 57, 58, 59, 60 and 61, wherein the one, two or three amino acid substitutions are selected from the group consisting of:
(A) substitution of the second amino acid from the N-terminus with an amino acid selected from the group consisting of threonine and serine;
(B) substitution of the third amino acid from the N-terminus with an amino acid selected from the group consisting of aspartic acid and glutamic acid; and
(C) substitution of the C-terminal amino acid with tyrosine.