Multimeric IL-15 soluble fusion molecules and methods of using same
View Patent ↗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 kit for the treatment of a neoplasia, the kit comprising an effective amount of an IL-15N72D:IL-15RαSu/Fc complex (Alt-803) comprising a dimeric IL-15RαSu/Fc and two IL-15N72D molecules and directions for its use, wherein said neoplasia is selected from the group consisting of multiple myeloma, beta-cell lymphoma, urothelial/bladder carcinoma and melanoma.
2. The kit of claim 1 , wherein said IL-15N72D:IL-15RαSu/Fc complex comprises:
(1) a dimer comprising two interleukin-15 (IL-15) receptor fusion polypeptides, wherein each IL-15 receptor fusion polypeptide comprises an IL-15 sushi-binding domain fused to an Fc domain (IL-15RαSu/Fc), and
(2) two variant interleukin-15 polypeptides comprising an N72D mutation (IL-15N72D polypeptides), wherein each interleukin-15 sushi-binding domain is bound to an IL-15N72D polypeptide.
3. The kit of claim 2 , wherein said IL-15RαSu/Fc comprises SEQ ID NO: 1.
4. The kit of claim 2 , wherein said IL-15N72D comprises SEQ ID NO: 2.
5. The kit of claim 1 , wherein said effective amount is between about 1 and about 20 μg/kg.
6. The kit of claim 1 , wherein said neoplasia is multiple myeloma.
7. The kit of claim 1 , wherein said neoplasia is beta-cell lymphoma.
8. The kit of claim 1 , wherein said neoplasia is urothelial/bladder carcinoma.
9. The kit of claim 1 , wherein said neoplasia is melanoma.