abstract |
The present invention provides multimeric IL-15 soluble fusion molecules and methods of making and using the same. Specifically, the present invention provides a soluble fusion protein complex comprising at least two soluble fusion proteins, wherein the first fusion protein comprises a) a first biologically active polypeptide covalently linked to b) an interleukin polypeptide or a functional fragment thereof; and the second fusion protein comprises c) a second biologically active polypeptide covalently linked to d) a soluble interleukin-15 receptor αIL-15Rα polypeptide or a functional fragment thereof; wherein the first and second fusion proteins have One or both further comprise an immunoglobulin Fc domain or functional fragment thereof; wherein the IL-15 domain of the first fusion protein binds to the soluble IL-15Rα domain of the second fusion protein to form a soluble fusion protein complex. The fusion protein complex of the present invention shows that it can mediate anti-tumor activity in animals, and has stronger anti-tumor efficacy than rhIL-15 administered at an equimolar dose. |