NKG2D-fc for immunotherapy
Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.
1. A method for treating cancer comprising:
administering to a subject having an NKG2D ligand expressing cancer a composition containing a chimeric NKG2D-Fc polypeptide and a pharmaceutically acceptable carrier, in an amount effective to treat the cancer, wherein the chimeric NKG2D-Fc polypeptide binds an NKG2D ligand, wherein the chimeric NKG2D-Fc polypeptide comprises an NKG2D extracellular domain, and wherein the chimeric NKG2D-Fc polypeptide does not include a variable domain of an antibody, a C H 1 domain of an antibody, or a light chain of an antibody.
2. The method of claim 1 , wherein the chimeric NKG2D-Fc polypeptide comprises a linking molecule which is not a contiguous portion of either NKG2D or Fc and which covalently joins an amino acid of NKG2D to an amino acid of Fc.
3. The method of claim 2 , wherein the linking molecule is a peptide linker.
4. The method of claim 3 , wherein the peptide linker is an IEGR (SEQ ID NO: 1) linker.
5. The method of claim 1 , wherein the chimeric NKG2D-Fc polypeptide is a recombinant fusion protein.
6. The method of claim 5 , wherein the NKG2D ligand expressing cancer is melanoma, lung cancer, plasma cell cancer, leukemia, lymphoma, ovarian cancer, colon cancer, pancreatic cancer or prostate cancer.
7. The method of claim 5 , further comprising treating the subject with an additional cancer therapy that is not the chimeric NKG2D-Fc polypeptide, wherein the additional cancer therapy is an immunotherapy, a radiation therapy or a chemotherapy.
8. The method of claim 7 , wherein the additional cancer therapy is a chemotherapy that damages DNA.
9. The method of claim 4 , wherein the chimeric NKG2D-Fc polypeptide comprises an NKG2D extracellular domain.
10. The method of claim 4 , wherein the chimeric NKG2D-Fc polypeptide is a recombinant fusion protein.
11. The method of claim 1 , wherein the chimeric NKG2D-Fc polypeptide comprises an activating Fc domain.
12. The method of claim 11 , wherein the activating Fc domain is an activating Fc domain of an IgG.
13. The method of claim 12 , wherein the IgG is IgG 1 .
14. The method of claim 1 , wherein the chimeric NKG2D-Fc polypeptide further comprises a signal sequence.