Fusion protein comprising IL-2 protein and CD80 protein, and use thereof
Provided is a fusion protein comprising IL-2 protein and CD80 protein. A fusion protein comprising CD80 fragment, immunoglobulin Fe, and an IL-2 variant can activate immune cells, such as natural killer cells, and at the same time, can control immune cell regulatory activity of regulatory T cells. Therefore, a pharmaceutical composition comprising the fusion protein as an active ingredient is very industrially useful in that such pharmaceutical composition can increase immune activity in the body, and thus can be effectively used against infectious diseases as well as cancer.
1. A fusion protein of the following structural formula (I) or (II):
N′-X-[linker (1)] n -Fc domain-[linker (2)] m ,-Y-C′ (I)
N′-Y-[linker (1)] n -Fc domain-[linker (2)] m ,-X-C′ (II)
in the structural formulas (I) and (II),
N′ is the N-terminus of the fusion protein,
C′ is the C-terminus of the fusion protein,
X is a CD80 protein,
Y is an IL-2 protein,
the linkers (1) and (2) are peptide linkers, and
n and m are each independently 0 or 1.
2. The fusion protein of claim 1 , wherein n and m are each independently 1.
3. The fusion protein of claim 1 , wherein the IL-2 protein comprises the amino acid sequence of SEQ ID NO: 10.
4. The fusion protein of claim 1 , wherein the IL-2 protein is an IL-2 variant.
5. The fusion protein of claim 4 , wherein the IL-2 variant is obtained by substitution of at least one selected from the 38 th 42 nd 45 th , 61 st , and 72 nd amino acids in the amino acid sequence of SEQ ID NO: 10.
6. The fusion protein of claim 4 , wherein the IL-2 variant comprises at least one substitution selected from the group consisting of R38A, F42A, Y45A, E61R, and L72G in the amino acid sequence of SEQ ID NO: 10.
7. The fusion protein of claim 4 , wherein the IL-2 variant comprises any one selected from the following substitution combinations (a) to (d) in the amino acid sequence of SEQ ID NO: 10:
(a) R38A/F42A
(b) R38A/F42A/Y45A
(c) R38A/F42A/E61R
(d) R38A/F42A/L72G.
8. The fusion protein of claim 4 , wherein the IL-2 variant comprises the amino acid sequence of SEQ ID NO: 6, 22, 23, or 24.
9. The fusion protein of claim 1 , wherein the CD80 protein comprises the amino acid sequence of SEQ ID NO: 11.
10. The fusion protein of claim 1 , wherein the CD80 protein is a CD80 fragment.
11. The fusion protein of claim 10 , wherein the CD80 fragment consists of the 35 th amino acid to 242 nd amino acid in the amino acid sequence of SEQ ID NO: 11.
12. The fusion protein of claim 1 , wherein the Fc domain is a wild type or variant.
13. The fusion protein of claim 1 , wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 4.
14. The fusion protein of claim 12 , wherein the variant of the Fc domain comprises the amino acid sequence of SEQ ID NO: 12.
15. The fusion protein of claim 1 , wherein the linker (1) is a peptide linker consisting of the amino acid sequence of SEQ ID NO: 3.
16. The fusion protein of claim 1 , wherein the linker (2) is a peptide linker consisting of the amino acid sequence of SEQ ID NO: 5.
17. The fusion protein of claim 1 , wherein the fusion protein comprises a sequence identity of 90% or higher to the amino acid sequence of SEQ ID NO: 9, 26, 28, or 30.
18. A fusion protein dimer wherein two fusion proteins of claim 1 are attached to each other.
19. The fusion protein dimer of claim 18 , wherein the fusion protein dimer is a homodimer.
20. A pharmaceutical composition comprising as an active ingredient:
the fusion protein of claim 1 or a dimer comprising two of the fusion protein attached to each other.
21. The pharmaceutical composition of claim 20 , further comprising a pharmaceutically acceptable carrier.