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 containing CD80 fragment, immunoglobulin Fc, 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 containing 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 polynucleotide encoding 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 polynucleotide of claim 1 , wherein n and m are each independently 1.
3. The polynucleotide of claim 1 , wherein the IL-2 protein comprises the amino acid sequence of SEQ ID NO: 10.
4. The polynucleotide of claim 1 , wherein the IL-2 protein is an IL-2 variant.
5. The polynucleotide of claim 4 , wherein the IL-2 variant is obtained by substitution of at least one selected from the 38th, 42nd, 45th, 61st, and 72nd amino acids in the amino acid sequence of SEQ ID NO: 10.
6. The polynucleotide 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 polynucleotide 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 polynucleotide of claim 4 , wherein the IL-2 variant comprises the amino acid sequence of SEQ ID NO: 6, 22, 23, or 24.
9. The polynucleotide of claim 1 , wherein the CD80 protein comprises the amino acid sequence of SEQ ID NO: 11.
10. The polynucleotide of claim 1 , wherein the CD80 protein is a CD80 fragment.
11. The polynucleotide of claim 10 , wherein the CD80 fragment consists of the 35th amino acid to 242nd amino acid in the amino acid sequence of SEQ ID NO: 11.
12. The polynucleotide of claim 1 , wherein the Fc domain is a wild type or variant.
13. The polynucleotide of claim 1 , wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 4.
14. The polynucleotide of claim 13 , wherein the variant of the Fc domain comprises the amino acid sequence of SEQ ID NO: 12.
15. The polynucleotide of claim 1 , wherein the linker (1) is a peptide linker consisting of the amino acid sequence of SEQ ID NO: 3.
16. The polynucleotide of claim 1 , wherein the linker (2) is a peptide linker consisting of the amino acid sequence of SEQ ID NO: 5.
17. The polynucleotide 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. The polynucleotide of claim 1 , wherein the polynucleotide has a sequence identity of 85% or higher to the nucleotide sequence of SEQ ID NO: 8, 25, 27, or 29.
19. A vector comprising the polynucleotide of claim 1 .
20. A transformed cell comprising the vector of claim 19 .