Cell expressing complexes of IL-15 and IL-15Ralpha
The present invention relates to agents that modulate interleukin-15 (“IL-15”) signal transduction or function (“Therapeutic Agents”) and the use ol″ those agents to modulate immune function. The Therapeutic Agents target the interaction between IL-15 and its receptor and modulate IL-15-induced signal transduction. The Therapeutic Agents may be formulated with polymers, such as poly-β-1-♦4-N-acetylglucosamine. for administration to a human subject to modulate IL-15-mediated immune function.
1. An isolated cell that recombinantly expresses any one of: (i) human IL-15 and a soluble form of human IL-15Ra at least 95% identical to the amino acid sequence comprising amino acid residues 31-267 of SEQ ID NO:3, (ii) a complex comprising human IL-15 and a soluble form of human IL-15Ra, wherein the human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31-267 of SEQ ID NO:3, wherein the cell expresses at least 0.15 pg of human IL-15 per day when cultured in serum-free media.
2. The cell of claim 1 , wherein the human IL-15 is at least 95% identical to the amino acid sequence comprising amino acid residues 49 to 162 of SEQ ID NO:1.
3. The cell of claim 1 , wherein the human IL-15 comprises the amino acid sequence of amino acid residues 49 to 162 of SEQ ID NO:1.
4. The cell of claim 1 , wherein the human IL-15Ra comprises the amino acid sequence of amino acid residues 31 to 267 of SEQ ID NO:3.
5. The cell of claim 1 , wherein the soluble form of human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31 to 205 of SEQ ID NO: 4.
6. The cell of claim 1 , wherein: (I) the human IL-15 is at least 95% identical to the amino acid sequence comprising amino acid residues 49 to 162 of SEQ ID NO:1; (II) the human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31 to 267 of SEQ ID NO:3.
7. The cell of claim 1 , wherein: (I) the human IL-15 is at least 95% identical to the amino acid sequence comprising amino acid residues 49 to 162 of SEQ ID NO:1; (II) the soluble form of human IL-15Ra is at least 95% identical to the amino acid sequence comprising amino acid residues 31 to 205 of SEQ ID NO:4.
8. The cell of claim 1 , wherein: (I) the human IL-15 consists of the amino acid sequence of amino acid residues 49 to 162 of SEQ ID NO:1; (II) the human IL-15Ra consists of the amino acid sequence of amino acid residues 31 to 267 of SEQ ID NO:3.
9. The cell of claim 1 , wherein the cell is an irradiated cancer cell.
10. The cell of claim 1 , wherein the cell is a mammalian cell line.
11. The cell of claim 1 , wherein the cell is from a 293H, 293 or CHO cell line.
12. The cell of claim 1 , wherein the cell expresses at least 0.6 pg of human IL-15 per day.
13. The cell of claim 1 , wherein the cell expresses at least 1 pg of human IL-15 per day.
14. The cell of claim 1 , wherein the cell expresses up to 2 pg of human IL-15 per day.
15. An isolated cell that recombinantly expresses a complex comprising human IL-15 and human IL-15Ra from a codon-optimized nucleic acid sequence encoding human IL-15 and a codon-optimized nucleic acid sequence encoding human IL-15Ra, wherein the human IL-15Ra is at least 95% identical to amino acid residues 31-267 of SEQ ID NO:14 or 31-205 of SEQ ID NO:16, wherein the cell expresses at least 0.15 pg of human IL-15 per day when cultured in serum-free media.
16. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 30 to 162 of SEQ ID NO:10; and the human IL15Ra comprises amino acid residues 31 to 267 of SEQ ID NO:14.
17. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 30 to 162 of SEQ ID NO:10; and the human IL15Ra comprises amino acid residues 31 to 205 of SEQ ID NO:16.
18. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 36 to 149 of SEQ ID NO:12; and the human IL15Ra comprises amino acid residues 31 to 267 of SEQ ID NO:14.
19. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 36 to 149 of SEQ ID NO:12; and the human IL15Ra comprises amino acid residues 31 to 205 of SEQ ID NO:16.
20. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 18 to 131 of SEQ ID NO:18; and the human IL15Ra comprises amino acid residues 31 to 267 of SEQ ID NO:14.
21. The isolated cell of claim 15 , wherein the human IL-15 comprises amino acid residues 18 to 131 of SEQ ID NO:18; and the human IL15Ra comprises amino acid residues 31 to 205 of SEQ ID NO:16.
22. The cell of claim 15 , wherein the cell is a mammalian cell line.
23. The cell of claim 15 , wherein the cell is from a 293H, 293 or CHO cell line.