INJECTABLE COMPOSITION
The present invention relates to a lyophilized preparation comprising two or more cancer antigen peptides derived from WT1 protein with an activity of inducing cytotoxic T lymphocytes for cancer peptide vaccine therapy.
1 : A lyophilized preparation comprising a WT1 killer peptide, a WT1 helper peptide and cyclodextrin, wherein the WT1 killer peptide comprises a compound selected from:
and
the WT1 helper peptide comprises a peptide consisting of the amino acid sequence:
(SEQ ID NO: 18)
WAPVLDFAPPGASAYGSL.
2 : The lyophilized preparation according to claim 1 , wherein the WT1 killer peptide is a compound of formula (3)
3 : The lyophilized preparation according to claim 1 , wherein the amounts of the WT1 helper peptide and cyclodextrin are 0.1 to 2.0 parts by weight and 0.2 to 5.0 parts by weight, respectively, relative to 1 part by weight of the WT1 killer peptide.
4 : The lyophilized preparation according to claim 1 , wherein the amounts of the WT1 helper peptide and cyclodextrin are 0.5 to 1.0 part by weight and 0.5 to 2.0 parts by weight, respectively, relative to 1 part by weight of the WT1 killer peptide.
5 : The lyophilized preparation according to claim 1 , wherein the cyclodextrin comprises at least one selected from the group consisting of α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), methyl-β-cyclodextrin (M-β-CD), sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and a pharmaceutically acceptable salt thereof.
6 : The lyophilized preparation according to claim 5 , wherein the cyclodextrin comprises at least selected from the group consisting of α-cyclodextrin (α-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and a pharmaceutically acceptable salt thereof.
7 : The lyophilized preparation according to claim 1 , wherein the cyclodextrin is hydroxypropyl-β-cyclodextrin (HP-β-CD) or a pharmaceutically acceptable salt thereof.
8 : The lyophilized preparation according to claim 1 , which further comprises at least one of arginine or methionine.
9 : The lyophilized preparation according to claim 8 , wherein the amount of arginine or methionine is 0.01 to 1.0 part by weight relative to 1 part by weight of the WT1 helper peptide.
10 : The lyophilized preparation according to claim 8 , wherein the amount of arginine or methionine is 0.1 to 0.5 part by weight relative to 1 part by weight of the WT1 helper peptide.
11 : The lyophilized preparation according to claim 10 , which comprises L-methionine as the methionine.
12 : The lyophilized preparation according to claim 1 , which further comprises an organic acid.
13 : The lyophilized preparation according to claim 12 , wherein the amount of the organic acid is 0.01 to 1.0 part by weight relative to 1 part by weight of the WT1 helper peptide.
14 : The lyophilized preparation according to claim 13 , wherein the amount of the organic acid is 0.05 to 0.5 part by weight relative to 1 part by weight of the WT1 helper peptide.
15 : The lyophilized preparation according to claim 12 , wherein the organic acid is at least one of tartaric acid or succinic acid.
16 : The lyophilized preparation according to claim 1 , which further comprises an adjuvant.
17 : The lyophilized preparation according to claim 16 , wherein the amount of the adjuvant is 1 to 500 parts by weight relative to 1 part by weight of the WT1 killer peptide.
18 : The lyophilized preparation according to claim 17 , wherein the amount of the adjuvant is 5 to 100 parts by weight relative to 1 part by weight of the WT1 killer peptide.
19 : The lyophilized preparation according to claim 16 , wherein the adjuvant is one of Freund's adjuvant, Montanide and W/O emulsion.
20 : The lyophilized preparation according to claim 19 , wherein the adjuvant is Montanide.
21 : The lyophilized preparation according to claim 1 produced by dissolving each ingredient in purified water in an amount of 0.5 to 2 mL per 5 mg of the WT1 killer peptide and lyophilizing the solution.