TRANSDERMAL CANCER ANTIGEN PEPTIDE PREPARATION
The invention enables more efficient CTL induction by applying a transdermal preparation containing a WT1 protein-derived cancer antigen peptide and an ether-type additive, which is liquid at 20° C., to a WT1 protein-derived cancer antigen peptide. The ether-type additive is represented by the formula (1): R 1 —O—R2 (1), wherein R 1 is a hydrocarbon group having 8-24 carbon atoms, and R 2 is a group represented by the formula (2): or a group represented by the formula (3): —(CH 2 CH 2 O) m H (3), wherein m is an integer of 1-18.
1 . A transdermal preparation comprising a WT1 protein-derived cancer antigen peptide, and an ether-type additive represented by the formula (1):
R 1 —O—R 2 (1)
[wherein R 1 is a hydrocarbon group having 8-24 carbon atoms, and
R 2 is a group represented by the formula (2):
or a group represented by the formula (3):
—(CH 2 CH 2 O) m H (3)
wherein m is an integer of 1-18],
wherein the additive is liquid at 20° C.
2 . The transdermal preparation according to claim 1 , wherein the WT1 protein-derived cancer antigen peptide is
a peptide comprising any amino acid sequence selected from the following amino acid sequences: Arg-Met-Phe-Pro-Asn-Ala-Pro-Tyr-Leu (SEQ ID NO: 2), Ser-Leu-Gly-Glu-Gln-Gln-Tyr-Ser-Val (SEQ ID NO: 3), Cys-Tyr-Thr-Trp-Asn-Gln-Met-Asn-Leu (SEQ ID NO: 4), and Ala-Leu-Leu-Pro-Ala-Val-Pro-Ser-Leu (SEQ ID NO: 5) or
a peptide comprising an altered amino acid sequence, which is any amino acid sequence selected from SEQ ID NOs: 2, 3, 4 and 5 but containing alteration of amino acid residue(s), and having a CTL induction activity.
3 . The transdermal preparation according to claim 1 or 2 , wherein the WT1 protein-derived cancer antigen peptide is a peptide shown in the amino acid sequence Arg-Met-Phe-Pro-Asn-Ala-Pro-Tyr-Leu (SEQ ID NO: 2).
4 . The transdermal preparation according to claim 1 , wherein the ether-type additive is represented by the formula (4):
[wherein R 1 is a hydrocarbon group having 8-24 carbon atoms, or the formula (5):
R 1 —O—(CH 2 CH 2 O) n H (5)
wherein R 1 is a hydrocarbon group having 8-24 carbon atoms, and
n is an integer of 2-18].
5 . The transdermal preparation according to claim 1 , wherein the ether-type additive is represented by the formula (6):
[wherein R 3 is a hydrocarbon group having 16-18 carbon atoms]
6 . The transdermal preparation according to claim 1 , wherein the ether-type additive is represented by the formula (7):
R 1 —O—(CH 2 CH 2 O) p H (7)
[wherein R 1 is a hydrocarbon group having 8-24 carbon atoms, and
p is an integer of 2-12].
7 . The transdermal preparation according to claim 6 , wherein R 1 is a branched alkyl group having 8-24 carbon atoms, a linear alkenyl group having 8-24 carbon atoms or a mixed alkyl group having 8-24 carbon atoms.
8 . The transdermal preparation according to claim 1 , wherein the ether-type additive is α-monoisostearyl glyceryl ether, monooleyl glyceryl ether, polyoxyethylene isostearyl ether which is liquid at 20° C., polyoxyethylene oleyl ether which is liquid at 20° C., polyoxyethylene alkyl (12-14) ether which is liquid at 20° C. or a mixture of these.
9 . The transdermal preparation according to claim 8 , wherein the ether-type additive is α-monoisostearyl glyceryl ether and/or monooleyl glyceryl ether.
10 . The transdermal preparation according to claim 1 , further comprising lactic acid.
11 . The transdermal preparation according to claim 10 , further comprising at least one kind of WT1 protein-derived cancer antigen peptide degradation inhibitor selected from the group consisting of decanoic acid, sodium deoxycholate or N-lauroylsarcosine.
12 . The transdermal preparation according to claim 1 , which has a dosage form of patches preparation, ointments, gels, creams, lotions or microneedle preparation.
13 . The transdermal preparation according to claim 8 , which is a patches preparation comprising a support and an adhesive layer formed on one surface of the support, wherein the adhesive layer comprises (1) WT1 protein-derived cancer antigen peptide, (2) at least one ether-type additive selected from the group consisting of α-monoisostearyl glyceryl ether, monooleyl glyceryl ether, polyoxyethylene isostearyl ether which is liquid at 20° C., polyoxyethylene oleyl ether which is liquid at 20° C. and polyoxyethylene alkyl (12-14) ether which is liquid at 20° C., and (3) an adhesive.
14 . A CTL inducer comprising a WT1 protein-derived cancer antigen peptide, and an ether-type additive represented by the formula (1):
R 1 —O—R 2 (1)
[wherein R 1 is a hydrocarbon group having 8-24 carbon atoms, and
R 2 is a group represented by the formula (2):
or a group represented by the formula (3):
—(CH 2 CH 2 O) m H (3)
wherein m is an integer of 1-18],
wherein the additive is liquid at 20° C.