Human antibodies specific for interleukin 15 (IL-15)
Isolated human monoclonal antibodies which specifically bind to IL-15 (e.g., human IL-15), and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced in a transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals, and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.
1. An isolated monoclonal antibody, or an antigen binding portion thereof, which binds IL-15 and inhibits IL-15 signaling through the IL-15 receptor, said antibody having a human heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:2.
2. An isolated monoclonal antibody, or an antigen binding portion thereof, which binds IL-15 and inhibits IL-15 signaling through the IL-15 receptor, said antibody having a human light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:4.
3. An isolated monoclonal antibody, or an antigen binding portion thereof, which binds an epitope on human IL-15 recognized by an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:2 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:4.
4. A composition comprising the antibody or antigen binding portion of claim 3 and a pharmaceutically acceptable carrier.
5. The composition of claim 4 further comprising a therapeutic agent selected from the group consisting of anti-inflammatory agents, disease-modifying anti-rheumatic drugs (DMARDS), immunosuppressive agents, chemotherapeutics agents for treating psoriasis, an anti-CD4 antibody, an anti-IL-2 antibody, and a tumor necrosis factor-α (TNF-α) inhibitor.
6. An immunoconjugate comprising the antibody or antigen binding portion of claim 3 and a therapeutic agent.
7. The immunoconjugate of claim 6 , wherein the therapeutic agent is an immunosuppressive agent.
8. The immunoconjugate of claim 6 , wherein the therapeutic agent is an anti-inflammatory agent selected from the group consisting of a steroidal anti-inflammatory agent, a nonsteroidal anti-inflammatory agent and a DMARD.
9. The immunoconjugate of claim 6 , wherein the therapeutic agent is a cytotoxic agent.
10. A composition comprising the immunoconjugate of claim 6 and a pharmaceutically acceptable carrier.