Compositions and methods for immunomodulation in an organism
The present invention relates to a therapeutic polypeptide and methods for its creation and use for modulating an immune response in a host organism in need thereof. In particular, the invention relates to the administration to an organism in need thereof, of an effective amount of a pre-coupled polypeptide complex comprising a lymphokine polypeptide portion, for example IL-15 (SEQ ID NO: 5, 6), IL-2 (SEQ ID NO: 10, 12) or combinations of both, and an interleukin receptor polypeptide portion, for example IL-15Ra (SEQ ID NO: 7, 8), IL-2Ra (SEQ ID NO: 9, 11) or combinations of both, for augmenting the immune system in, for example, cancer, SCID, AIDS, or vaccination; or inhibiting the immune system in, for example, rheumatoid arthritis, or Lupus. The therapeutic complex of the invention surprisingly demonstrates increased half-life, and efficacy in vivo.
1. A polypeptide complex comprising an interleukin 15 (IL-15) polypeptide or portion thereof, wherein said IL-15 polypeptide or portion thereof has a primary amino acid structure with at least 90% homology to SEQ ID NO: 6 and an interleukin 15 receptor alpha (IL-15Ra) polypeptide or portion thereof capable of binding said interleukin 15 polypeptide, wherein said IL-15Ra polypeptide or portion thereof has a primary amino acid structure with at least 90% homology to SEQ ID NO: 8 and wherein said interleukin 15 polypeptide and said interleukin 15 receptor alpha polypeptide are pre-coupled wherein said polypeptide complex increases T cell proliferation.
2. The polypeptide complex of claim 1 , wherein said interleukin 15 polypeptide further comprises a heterologous signal peptide sequence on the amino terminus.
3. The polypeptide complex of claim 1 , wherein the pre-coupled complex has an in vivo half-life of at least one-hour.
4. The polypeptide complex of claim 1 , wherein the complex comprises an interleukin 15 polypeptide and an interleukin 15 receptor alpha polypeptide or portion thereof within a single polypeptide chain.
5. The polypeptide complex of claim 1 , wherein the IL-15 polypeptide does not contain a signal sequence.
6. The polypeptide complex of claim 1 , wherein the IL-15 receptor alpha polypeptide is a soluble form.
7. The polypeptide complex of claim 1 , wherein the complex is expressed in a CHO cell.
8. The polypeptide complex of claim 7 , wherein at least 0.5%, 1%, 2%, 3%, 5% or more of each polypeptide in the complex have an α2,3-linked sialic acid residue.
9. The complex of claim 7 , wherein none of the polypeptides in the complex comprise a bisecting GlcNAc.