IL-15-based fusions to IL-12 and IL-18
The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.
1. An isolated fusion protein complex comprising: a first soluble protein comprising an interleukin-15 (IL-15) polypeptide domain and an IL-18 polypeptide domain, and a second soluble protein comprising a soluble IL-15 receptor alpha sushi (IL-15RαSu) polypeptide domain and an IL-12 polypeptide domain,
wherein the IL-15 polypeptide domain binds to the IL-15RαSu polypeptide domain to form the soluble fusion protein complex.
2. The soluble fusion protein complex of claim 1 , wherein the IL-15 polypeptide is an IL-15 variant comprising an N72D mutation (IL-15N72D).
3. The soluble fusion protein complex of claim 1 , wherein the IL-12 polypeptide domain comprises the p40 and p35 subunits of IL-12.
4. The soluble fusion protein complex of claim 3 , wherein the p40 and p35 subunits are linked by a flexible polypeptide linker into a single-chain format.
5. A soluble fusion protein complex comprising two soluble fusion protein complexes of claim 1 covalently linked together.