Method of treating neoplasia with a multimeric IL-15 soluble fusion molecule
The present invention features compositions and methods featuring ALT-803, a complex of an interleukin-15 (IL-15) superagonist mutant and a dimeric IL-15 receptor α/Fc fusion protein useful for enhancing an immune response against a neoplasia (e.g., multiple myeloma, melanoma, lymphoma) or a viral infection (e.g., human immunodeficiency virus).
1. A method for treating neoplasia in a subject in need thereof, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising an interleukin-15N72D:IL-15 receptor alpha Sushi/Fc (IL-15N72D:IL-15RαSu/Fc) complex, wherein the complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules (ALT-803).
2. The method of claim 1 , wherein the IL-15RαSu/Fc comprises SEQ ID NO: 1.
3. The method of claim 1 , wherein the IL-15N72D molecule comprises SEQ ID NO: 2.
4. The method of claim 1 , wherein the neoplasia is multiple myeloma.
5. The method of claim 1 , wherein the effective amount is between about 1 and 20 μg/kg.
6. The method of claim 5 , wherein the effective amount is about 1 μg/kg.
7. The method of claim 6 , wherein the effective amount is 10 μg/week.
8. The method of claim 1 , wherein the effective amount is between about 20 μg and 100 μg/kg.
9. The method of claim 8 , wherein the effective amount is 30 μg/kg.
10. The method of claim 1 , wherein Alt-803 is administered once, twice, or three times per week.
11. The method of claim 1 , wherein the pharmaceutical composition is administered systemically, intravenously, or by instillation.
12. The method of claim 1 , wherein the neoplasia is beta cell lymphoma.
13. The method of claim 1 , wherein the neoplasia is urothelial/bladder carcinoma.
14. The method of claim 1 , wherein the neoplasia is melanoma.
15. The method of claim 5 , wherein the effective amount is about 5 μg/kg.
16. The method of claim 5 , wherein the effective amount is about 10 μg/kg.
17. The method of claim 5 , wherein the effective amount is about 15 μg/kg.
18. The method of claim 5 , wherein the effective amount is about 20 μg/kg.
19. The method of claim 8 , wherein the effective amount is about 50 μg/kg.
20. The method of claim 8 , wherein the effective amount is about 75 μg/kg.
21. The method of claim 8 , wherein the effective amount is about 100 μg/kg.