Pharmaceutical composition comprising immunoglobulin Fc-fused interleukin-7 fusion protein for preventing or treating human papillomavirus-caused diseases
The present invention relates to a pharmaceutical composition comprising an immunoglobulin Fc region and an IL-7 fusion protein. Specifically, when a fusion protein comprising the immunoglobulin Fc region and IL-7 is administered to an affected area, a strong immune response is induced in the body and thus allows human papillomavirus-caused diseases to be prevented or treated.
1. A method for treating a genital disease in a subject in need thereof, comprising administering to the subject an effective amount of an interleukin-7 (IL-7) fusion protein,
wherein the genital disease is a human papillomavirus infection or cervical cancer,
wherein the administration is a local administration,
wherein the IL-7 fusion protein comprises a modified IL-7 and an immunoglobulin Fc region,
wherein the modified IL-7 has the following structure:
A-IL-7,
wherein
the A is an oligopeptide consisting of 1 to 10 amino acid residues selected from the group consisting of glycine and methionine, with proviso that when A is an oligopeptide of 1 amino acid residue, A is glycine; and
the IL-7 of the structure A-IL-7 is (i) an IL-7 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-6 or (ii) a peptide having an amino sequence which has a sequence identity of 95% or greater to the sequence set forth in SEQ ID NO: 1, and
wherein the immunoglobulin Fc region has the following Formula (I)
N′-(Z1) p -(Y) q -Z2-Z3-Z4-C′ Formula (I)
wherein
N′ is the N-terminus of a polypeptide and C′ is the C-terminus of the polypeptide,
p or q is an integer of 0 or 1,
Z1 is an amino acid sequence comprising 5 to 9 consecutive amino acid residues in the N-terminus direction starting from the 98th position of SEQ ID NO: 7,
Y is an amino acid sequence comprising 5 to 64 consecutive amino acid residues in the N-terminus direction starting from the 162nd position of SEQ ID NO: 7,
Z2 is an amino acid sequence comprising 4 to 37 consecutive amino acid residues in the C-terminus direction starting from the 163rd position of SEQ ID NO: 7,
Z3 is an amino acid sequence comprising 70 to 106 consecutive amino acid residues in the N-terminus direction starting from the 220th position of SEQ ID NO: 8, and
Z4 is an amino acid sequence comprising 80 to 107 consecutive amino acid residues in the C-terminus direction starting from the 221st position of SEQ ID NO: 8.
2. The method of claim 1 , wherein the local administration is a mucosal administration.
3. The method of claim 1 , wherein the IL-7 is fused to the N-terminus or C-terminus of the immunoglobulin Fc region.
4. The method of claim 1 , wherein the IL-7 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 6.
5. The method of claim 1 , wherein the A is selected from the group consisting of glycine, methionine-methionine, glycine-glycine, methionine-glycine, glycine-methionine, methionine-methionine-methionine, methionine-methionine-glycine, methionine-glycine-methionine, glycine-methionine-methionine, methionine-glycine-glycine, glycine-methionine-glycine, glycine-glycine-methionine, methionine-methionine-methionine, and glycine-glycine-glycine.
6. The method of claim 1 , wherein the modified immunoglobulin Fc region is selected from the group consisting of SEQ ID NO: 9 to 14.
7. The method of claim 1 , wherein the oligopeptide A consists of 1 to 5 amino acid residues selected from the group consisting of glycine and methionine.
8. The method of claim 1 , wherein the IL-7 is fused to the N-terminus of the immunoglobulin Fc region.
9. A method for treating a human papillomavirus infection or cervical cancer in a subject in need thereof, comprising administering to the subject an effective amount of an interleukin-7 (IL-7) fusion protein via a mucosal administration,
wherein the IL-7 fusion protein comprises an IL-7 and an immunoglobulin Fc region,
wherein the IL-7 is any one of the following (i)-(iii):
(i) an IL-7 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-6;
(ii) a peptide having an amino sequence which has a sequence identity of 95% or greater to the sequence set forth in SEQ ID NO: 1; and
(iii) a modified IL-7 having the following structure:
A-IL-7,
wherein
the A is an oligopeptide consisting of 1 to 10 amino acid residues selected from the group consisting of glycine and methionine, with proviso that when A is an oligopeptide of 1 amino acid residue, A is glycine; and
the IL-7 is the IL-7 of (i) or the peptide of (ii), and
wherein the immunoglobulin Fc region has the following formula (I)
N′-(Z1) p -(Y) q -Z2-Z3-Z4-C′ Formula (I)
wherein
N′ is the N-terminus of a polypeptide and C′ is the C-terminus of the polypeptide,
p or q is an integer of 0 or 1,
Z1 is an amino acid sequence comprising 5 to 9 consecutive amino acid residues in the N-terminus direction starting from the 98th position of SEQ ID NO: 7,
Y is an amino acid sequence comprising 5 to 64 consecutive amino acid residues in the N-terminus direction starting from the 162nd position of SEQ ID NO: 7,
Z2 is an amino acid sequence comprising 4 to 37 consecutive amino acid residues in the C-terminus direction starting from the 163rd position of SEQ ID NO: 7,
Z3 is an amino acid sequence comprising 70 to 106 consecutive amino acid residues in the N-terminus direction starting from the 220th position of SEQ ID NO: 8, and
Z4 is an amino acid sequence comprising 80 to 107 consecutive amino acid residues in the C-terminus direction starting from the 221st position of SEQ ID NO: 8.
10. The method of claim 9 , wherein the IL-7 is fused to the N-terminus or C-terminus of the immunoglobulin Fc region.
11. The method of claim 9 , wherein the IL-7 is the (iii) modified IL-7.
12. The method of claim 9 , wherein the IL-7 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 6.
13. The method of claim 9 , wherein the A is selected from the group consisting of glycine, methionine-methionine, glycine-glycine, methionine-glycine, glycine-methionine, methionine-methionine-methionine, methionine-methionine-glycine, methionine-glycine-methionine, glycine-methionine-methionine, methionine-glycine-glycine, glycine-methionine-glycine, glycine-glycine-methionine, methionine-methionine-methionine, and glycine-glycine-glycine.
14. The method of claim 9 , wherein the modified immunoglobulin Fc region is selected from the group consisting of SEQ ID NO: 9 to 14.
15. The method of claim 9 , wherein the oligopeptide A consists of 1 to 5 amino acid residues selected from the group consisting of glycine and methionine.
16. The method of claim 9 , wherein the IL-7 is fused to the N-terminus of the immunoglobulin Fc region.