Composition for preventing or treating benign tumor
The present disclosure provides a composition for preventing or treating a benign tumor. Provided is a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a specific embodiment, the present disclosure provides a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a preferred embodiment, the composition for preventing or treating a benign tumor (e.g. familial adenomatous polyposis) according to the present disclosure comprises a killer type WT1 peptide and/or a helper type WT1 peptide. In a further preferred embodiment, the WT1 peptide is WT1 126 killer peptide and/or WT1 35 helper peptide. In another aspect, provided are a method of inducing WT1 peptide-specific CTLs, a method of inducing WT1-specific helper T cells, and a method of inducing dendritic cells presenting a WT1 peptide.
1. A method for treating a benign tumor expressing WT1 selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in a subject, the method comprising:
administering to the subject an effective amount of a peptide selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNOMNL of SEQ ID NO: 45,
CMTWNQMNL of SEQ ID NO: 3,
C-CYTWNQMNL of SEQ ID NO: 47 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond, and
C-CMTWNQMNL of SEQ ID NO: 48 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond.
2. The method according to claim 1 , wherein the method comprises administering a peptide selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNQMNL of SEQ ID NO: 45,
and
CMTWNQMNL of SEQ ID NO: 3.
3. A method for treating a benign tumor expressing WT1 selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in a subject, the method comprising:
administering to the subject an effective amount of a conjugate of formula (2) or a conjugate of formula (3),
wherein C-C shown in the formulas (2) and (3) means that the C residues are linked together by a disulfide bond.
4. The method 3 , wherein the method comprises
administering the conjugate of formula (3),
5. The method according to claim 1 , further comprising:
administering at least one peptide selected from the group consisting of
WAPVLDFAPPGASAYGSL of SEQ ID NO: 4,
CWAPVLDFAPPGASAYGSL of SEQ ID NO: 50
and
WAPVLDFAPPGASAYGSLC of SEQ ID NO: 51.
6. The method according to claim 3 , wherein the method comprises administering the conjugate of formula (2), and
a peptide WAPVLDFAPPGASAYGSL of SEQ ID NO: 4.
7. The method according to claim 4 , wherein the method comprises administering the conjugate of formula (3), and
a peptide WAPVLDFAPPGASAYGSL of SEQ ID NO: 4.
8. The method according claim 1 , wherein the method further comprises administering an adjuvant.
9. The method according to claim 8 , wherein the adjuvant is Montanide® ISA51 adjuvant.
10. The method according to claim 1 , wherein the benign tumor is selected from the group consisting of familial adenomatous polyposis, and non-hereditary colorectal adenoma.
11. The method according to claim 10 , wherein the benign tumor is familial adenomatous polyposis.
12. The method according to claim 1 , wherein the administering is once a week.
13. A method for treating a benign tumor expressing WT1 selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in a subject, the method comprising:
administering to the subject an effective amount of a nucleic acid molecule encoding a peptide selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNQMNL of SEQ ID NO: 45,
CMTWNQMNL of SEQ ID NO: 3,
C-CYTWNQMNL of SEQ ID NO: 47 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond, and
C-CMTWNQMNL of SEQ ID NO: 48 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond.
14. The method according to claim 13 , wherein the nucleic acid molecule includes RNA and/or DNA.
15. The method according to claim 13 , wherein the benign tumor is selected from the group consisting of familial adenomatous polyposis, and non-hereditary colorectal adenoma.
16. The method according to claim 15 , wherein the benign tumor is familial adenomatous polyposis.
17. The method according to claim 13 , wherein the method comprises administering the nucleic acid molecule once a week.
18. A method, comprising:
culturing peripheral blood mononuclear cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in the presence of a peptide; and
inducing WT1-specific CTLs and/or WT1-specific helper T cells from the peripheral blood mononuclear cells,
wherein the peptide is selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNOMNL of SEQ ID NO: 45,
CMTWNQMNL of SEQ ID NO: 3,
C-CYTWNQMNL of SEQ ID NO: 47 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond, and
C-CMTWNQMNL of SEQ ID NO: 48 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond.
19. The method according to claim 18 , further comprising administering to the subject an effective amount of the WT1-specific CTLs and/or WT1-specific helper T cells.
20. A method, comprising:
culturing immature dendritic cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in the presence of a peptide; and
inducing WT1-presenting dendritic cells,
wherein the peptide is selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNOMNL of SEQ ID NO: 45,
CMTWNQMNL of SEQ ID NO: 3,
C-CYTWNQMNL of SEQ ID NO: 47 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond, and
C-CMTWNQMNL of SEQ ID NO: 48 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond.
21. The method according to claim 20 , further comprising:
administering to the subject an effective amount of the WT1-presenting dendritic cells.
22. A method, comprising:
culturing peripheral blood mononuclear cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in the presence of a conjugate of formulas (2) or (3); and
inducing WT1-specific CTLs and/or WT1-specific helper T cells from the peripheral blood mononuclear cells,
wherein the conjugate of the formula (2) is
and the conjugate of the formula (3) is
wherein C-C shown in the formulas (2) and (3) means that the C residues are linked together by a disulfide bond.
23. The method according to claim 22 , further comprising:
administering to the subject an effective amount of the WT1-specific CTLs and/or WT1-specific helper T cells.
24. A method, comprising:
culturing immature dendritic cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma in the presence of a conjugate of formulas (2) or (3); and
inducing WT1-presenting dendritic cells,
wherein the conjugate of the formula (2) is
and the conjugate of the formula (3) is
wherein C-C shown in the formulas (2) and (3) means that the C residues are linked together by a disulfide bond.
25. A method, comprising:
introducing a nucleic acid molecule, which encodes a peptide into peripheral blood mononuclear cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma; and
inducing WT1-specific CTLs and/or WT1-specific helper T cells from the peripheral blood mononuclear cells,
wherein the peptide is selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNQMNL of SEQ ID NO: 45,
CMTWNQMNL of SEQ ID NO: 3,
C-CYTWNQMNL of SEQ ID NO: 47 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond, and
C-CMTWNQMNL of SEQ ID NO: 48 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond.
26. A method, comprising:
introducing a nucleic acid molecule, which encodes a conjugate of formulas (2) or (3) into peripheral blood mononuclear cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma; and
inducing WT1-specific CTLs and/or WT1-specific helper T cells from the peripheral blood mononuclear cells,
wherein the conjugate of the formula (2) is
and the conjugate of the formula (3) is
wherein C-C shown in the formulas (2) and (3) means that the C residues are linked together by a disulfide bond.
27. A method, comprising:
introducing a nucleic acid molecule, which encodes a peptide into immature dendritic cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma; and
inducing WT1-presenting dendritic cells,
wherein the peptide is selected from the group consisting of
RMFPNAPYL of SEQ ID NO: 2,
RYFPNAPYL of SEQ ID NO: 46,
YMFPNAPYL of SEQ ID NO: 14,
CYTWNQMNL of SEQ ID NO: 45,
CMTWNQMNL of SEQ ID NO: 3,
C-CYTWNQMNL of SEQ ID NO: 47 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond, and
C-CMTWNQMNL of SEQ ID NO: 48 wherein C-C shown in the formula means that the C residues are linked together by a disulfide bond.
28. A method, comprising:
introducing a nucleic acid molecule, which encodes a conjugate of formulas (2) or (3) into immature dendritic cells from a subject in need of treatment for a benign tumor selected from the group consisting of familial adenomatous polyposis, non-hereditary colorectal adenoma, intraductal papillary mucinous neoplasm, meningioma, schwannoma, epithelial adenoma of an organ, papilloma, non-epithelial myoma, lipoma, and chondroma; and
inducing WT1-presenting dendritic cells,
wherein the conjugate of the formula (2) is
and the conjugate of the formula (3) is
wherein C-C shown in the formulas (2) and (3) means that the C residues are linked together by a disulfide bond.