WT1 antigen peptide conjugate vaccine
A compound represented by the formula (1): wherein X a and Y a are each a single bond and the like, cancer antigen peptide A is an MHC class I-restricted WT1 peptide consisting of 7-30 amino acid residues, R 1 is a hydrogen atom, a group represented by the formula (2): wherein X b and Y b are each a single bond and the like, cancer antigen peptide B has a sequence different from that of the cancer antigen peptide A, and is an MHC class I-restricted WT1 peptide consisting of 7-30 amino acid residues, or cancer antigen peptide C, and cancer antigen peptide C has a sequence different from that of the cancer antigen peptide A, and is an MHC class I-restricted WT1 peptide or an MHC class II-restricted WT1 peptide, consisting of 7-30 amino acid residues containing one cysteine residue, or a salt thereof, and the like.
1. A compound of Formula (1-2) or a pharmaceutically acceptable salt thereof
wherein:
X a and Y a are each a single bond;
X b and Y b are each independently a single bond or a divalent peptide group consisting of 1-4 amino acid residues wherein X b and Y b together have 0-4 amino acid residues;
cancer antigen peptide A and cancer antigen peptide B are different and each is a peptide consisting of an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 2)
RMFPNAPYL,
(SEQ ID NO: 3)
CMTWNQMNL,
(SEQ ID NO: 5)
ALLPAVPSL,
(SEQ ID NO: 6)
SLGEQQYSV,
(SEQ ID NO: 7)
RVPGVAPTL,
and
a peptide consisting of an amino acid sequence selected from SEQ ID NOs: 2, 3, 5, 6 and 7 wherein 1 amino acid is substituted, and having a cytotoxic T cell (CTL) induction activity,
wherein the alpha amino group of the N-terminal amino acid of the cancer antigen peptide A binds to Y a and the backbone carbonyl group of the C-terminal amino acid of the cancer antigen peptide A binds to the hydroxyl group; and
wherein the alpha amino group of the N-terminal amino acid of the cancer antigen peptide B binds to Y b and the backbone carbonyl group of the C-terminal amino acid of the cancer antigen peptide B binds to the hydroxyl group.
2. The compound according to claim 1 , wherein the compound of the formula (1) is a compound of formula (3):
wherein the bond between C and C is a disulfide bond and wherein the peptides in formula (3) correspond to SEQ ID NOs:245 and 246, respectively,
or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 , wherein the cancer antigen peptide A is
a peptide consisting of an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 2)
RMFPNAPYL,
(SEQ ID NO: 3)
CMTWNQMNL,
(SEQ ID NO: 4)
CYTWNQMNL,
(SEQ ID NO: 5)
ALLPAVPSL,
(SEQ ID NO: 6)
SLGEQQYSV
and
(SEQ ID NO: 7)
RVPGVAPTL,
or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1 , wherein X b is a single bond, and Y b is a single bond or an alanine residue, or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 , wherein the cancer antigen peptide B is a peptide consisting of an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 2)
RMFPNAPYL,
(SEQ ID NO: 3)
CMTWNQMNL,
(SEQ ID NO: 4)
CYTWNQMNL,
(SEQ ID NO: 5)
ALLPAVPSL,
(SEQ ID NO: 6)
SLGEQQYSV,
and
(SEQ ID NO: 7)
RVPGVAPTL,
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition, comprising:
the compound according to claim 1 or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
7. The pharmaceutical composition according to claim 6 , which is a cancer vaccine.
8. A method for treating or preventing WT1 positive cancer, comprising:
administering a therapeutically or prophylactically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof, to a WT1 positive cancer patient in need thereof.
9. A method of obtaining two different MHC class I-restricted epitopes, or an MHC class I-restricted epitope and an MHC class II-restricted epitope, comprising:
reacting the compound according to claim 1 or a pharmaceutically acceptable salt thereof with ERAP1.
10. A composition comprising:
a compound of formula (3):
and wherein the peptides in formula (3) correspond to SEQ ID NOs: 245 and 246, respectively wherein the bond between C and C is a disulfide bond; and
a peptide consisting of an amino acid sequence selected from the group consisting of:
(SEQ ID NO: 22)
CNKRYFKLSHLQMHSRK,
(SEQ ID NO: 23)
CNKRYFKLSHLQMHSRKH,
(SEQ ID NO: 24)
CNKRYFKLSHLQMHSRKHTG,
(SEQ ID NO: 244)
WAPVLDFAPPGASAYGSL,
(SEQ ID NO: 242)
CWAPVLDFAPPGASAYGSL
and
(SEQ ID NO: 243)
WAPVLDFAPPGASAYGSLC.
11. A pharmaceutical composition comprising:
the composition according to claim 10 ; and a pharmaceutically acceptable carrier.
12. The pharmaceutical composition according to claim 11 , which is a cancer vaccine.
13. A method for treating or preventing WT1 positive cancer, comprising:
administering a therapeutically or prophylactically effective amount of the composition according to claim 10 to a WT1 positive cancer patient in need thereof.