IL-15-BASED MOLECULES AND METHODS OF USE THEREOF
The invention features combination therapies using an IL-15-based superagonist complex and an antibody to effectively treat subjects with cancer and infectious diseases.
1 .- 30 . (canceled)
31 . A kit for use in treating a neoplasia in a subject, the kit comprising:
a first vial comprising an effective amount of an antibody formulated for administration to the subject, wherein said antibody is an immune checkpoint inhibitor;
a second vial comprising an effective amount of an IL-15N72D:IL-15RαSu/Fc complex (ALT-803) formulated for administration to a subject, wherein said ALT-803 comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules; and
instructions for said use thereof.
32 . The kit of claim 31 , wherein the IL-15N72D molecule comprises the amino acid sequence of SEQ ID NO: 3.
33 . The kit of claim 31 , wherein the IL-15RαSu/Fc comprises the amino acid sequence of SEQ ID NO: 6.
34 . The kit of claim 31 , wherein the ALT-803 is formulated for administration to the subject at 0.1 μg/kg to 1 mg/kg.
35 . The kit of claim 34 , wherein the ALT-803 is formulated for administration to the subject at 15 μg/kg.
36 . The kit of claim 31 , wherein the antibody comprises an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, an anti-programmed cell death-1 (PD-1) antibody, a SLAMF7 antibody, or an anti-programmed cell death-ligand 1 (PD-L1) antibody.
37 . The kit of claim 31 , wherein the antibody is selected from the group consisting of ipilimumab, nivolumab, pembrolizumab, and durvalumab.
38 . A kit for use in treating a neoplasia in a subject, the kit comprising:
a first vial comprising an effective amount of an antibody formulated for administration to the subject, wherein said antibody is a tumor-specific antibody;
a second vial comprising an effective amount of an IL-15N72D:IL-15RαSu/Fc complex (ALT-803) formulated for administration to a subject, wherein said ALT-803 comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules; and
instructions for said use thereof.
39 . The kit of claim 38 , wherein the IL-15N72D molecule comprises the amino acid sequence of SEQ ID NO: 3.
40 . The kit of claim 38 , wherein the IL-15RαSu/Fc comprises the amino acid sequence of SEQ ID NO: 6.
41 . The kit of claim 38 , wherein the ALT-803 is formulated for administration to the subject at 0.1 μg/kg to 1 mg/kg.
42 . The kit of claim 41 , wherein the ALT-803 is formulated for administration to the subject at 15 μg/kg.
43 . The kit of claim 38 , wherein said antibody is specific for a tumor antigen selected from the group consisting of CD20, GP75, HER2, EGFR, CD30, CD33, CD38, and VEGF.
44 . The kit of claim 38 , wherein the antibody is selected from the group consisting of rituximab, daratumumab, cetuximab, elotuzumab, and bevacizumab.
45 . A kit for use in treating a neoplasia in a subject, the kit comprising:
a first vial comprising an effective amount of Bacille Calmette-Guerin (BCG) formulated for administration to the subject;
a second vial comprising an effective amount of an IL-15N72D:IL-15RαSu/Fc complex (ALT-803) formulated for administration to a subject, wherein said ALT-803 comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules; and
instructions for said use thereof.
46 . The kit of claim 45 , wherein the IL-15N72D molecule comprises the amino acid sequence of SEQ ID NO: 3.
47 . The kit of claim 45 , wherein the IL-15RαSu/Fc comprises the amino acid sequence of SEQ ID NO: 6.
48 . The kit of claim 45 , wherein the effective amount of said ALT-803 is between 5 ag and 1000 μg.
49 . The kit of claim 48 , wherein the effective amount of said ALT-803 is 400 μg.
50 . The kit of claim 45 , wherein the effective amount of BCG is 50 mg.