IL-15Ralpha sushi domain—IL-15 fusion proteins
The present invention relates to the stimulation of the IL-15Rbeta/gamma signalling pathway, to thereby induce and/or stimulate the activation and/or proliferation of IL-15Rbeta/gamma-positive cells, such as NK and/or T cells. Appropriate compounds include compounds comprising at least one IL-15Rbeta/gamma binding entity, directly or indirectly linked by covalence to at least one polypeptide which contains the sushi domain of the extracellular region of an IL-15Ralpha.
1. A fusion protein comprising an IL-15Rα sushi domain and an IL-15, which are joined by a flexible linker consisting of the amino acid sequence of SEQ ID NO:50, wherein the fusion protein is an IL-15 agonist.
2. The fusion protein of claim 1 , wherein the IL-15 receptor alpha IL-15Rα sushi domain polypeptide consists of the amino acid sequence of SEQ ID NO: 14.
3. The fusion protein of claim 1 , wherein the IL-15 is a human IL-15.
4. A pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier.
5. A fusion protein comprising an IL-15Rα sushi domain and an IL-15, which are joined by a flexible linker consisting of the amino acid sequence of SEQ ID NO: 52, wherein the fusion protein is an IL-15 agonist.
6. The fusion protein of claim 5 , wherein the IL-15 receptor alpha IL-15Rα sushi domain polypeptide consists of the amino acid sequence of SEQ ID NO: 14.
7. The fusion protein of claim 5 , wherein the IL-15 is a human IL-15.
8. A pharmaceutical composition comprising the fusion protein of claim 5 and a pharmaceutically acceptable carrier.
9. A fusion protein comprising a human IL-15Rα sushi domain and a human IL-15, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO:60.
10. A pharmaceutical composition comprising the fusion protein of claim 9 and a pharmaceutically acceptable carrier.