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. A method for killing diseased cells expressing a target antigen, the method comprising:
treating immune cells with an effective amount of an IL-15N72D:IL-15RaSu/Fc complex (ALT-803),
mixing the ALT-803-treated immune cells with an antibody specific to a target antigen and diseased cells expressing said target antigen,
killing the diseased cells via ADCC or ADCP mediated by the ALT-803-treated immune cells and target antigen-specific antibody.
2. The method of claim 1 , wherein the level of diseased cell killing is increased by at least 5% compared to that mediated by immune cells that were not treated with ALT-803.
3. The method of claim 1 , wherein the IL-15N72D molecule comprises SEQ ID NO: 3.
4. The method of claim 1 , wherein the IL-15RaSu/Fc comprises SEQ ID NO: 6.
5. The method of claim 1 , wherein said antibody is a tumor-specific antibody or an antiviral antibody.
6. The method of claim 1 , wherein said antibody is an immune-checkpoint inhibitor.
7. The method of claim 1 , wherein said antibody comprises an anti-gp75 antibody, an anti-CD20 antibody, an anti-HER2 antibody, an anti-EGFR antibody, an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, an anti-programmed cell death-1 (PD-1) antibody, an anti-programmed cell death-ligand 1 (PD-L1) antibody, or an anti-programmed cell death-ligand 2(PD-L2) antibody.