Methods of treating cancer using il-21

Abstract

Methods for treating mammals with cancer using molecules that have an IL-21 functional activity are described. The molecules having IL-21 functional activities include polypeptides that have homology to the human IL-21 polypeptide sequence and proteins fused to a polypeptide with IL-21 functional activity. The molecules can be used as a monotherapy or in combination with other known cancer therapeutics.

1 . A method for treating cancer comprising administering to a patient a polypeptide having a functional activity of IL-21 wherein the polypeptide has at least 80% identity to an IL-21 polypeptide comprising residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2, and
 wherein the cancer is selected from the group consisting of epithelial carcinoma, bone sarcoma, neuroblastoma, stomach cancer, Hodgkin's lymphoma, myeloid leukemia, lymphocytic leukemia and chronic lymphocytic leukemia   
     
     
         2 . The method of  claim 1 , wherein the polypeptide has at least 90% identity to an IL-21 polypeptide comprising residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2. 
     
     
         3 . The method of  claim 1 , wherein the polypeptide has at least 95% identity to an IL-21 polypeptide comprising residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2. 
     
     
         4 . The method of  claim 1 , wherein the polypeptide comprises residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2 
     
     
         5 . The method of  claim 1 , wherein the polypeptide is fused to a second polypeptide. 
     
     
         6 . The method of  claim 1 , wherein the polypeptide is conjugated to a toxic compound. 
     
     
         7 . The method of  claim 6 , wherein the toxic compounds is selected from the group consisting of a small molecule drug, a radioisotope, and a naturally occurring protein toxin. 
     
     
         8 . The method of  claim 1 , further comprising administering an immune modulator selected from the group consisting of a cytokine, interferon alpha, a chemotherapeutic agent, radiation and myeloablation. 
     
     
         9 . The method of  claim 1 , further comprising administering a tumor vaccine. 
     
     
         10 . The method of  claim 1 , further comprising administering a monoclonal antibody. 
     
     
         11 . The method of  claim 1 , wherein the treatment results in a tumor response measured as complete response or partial response. 
     
     
         12 . A method for treating cancer comprising administering to a patient a polypeptide having a functional activity of IL-21 and a monoclonal antibody,
 wherein the polypeptide has at least 80% identity to an IL-21 polypeptide comprising residue 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2, and   wherein the cancer is selected from the group consisting of renal cell carcinoma, breast cancer, glioma, colon cancer, epithelial carcinoma, prostate cancer, ovarian cancer, sarcoma of the soft tissue, sarcoma of the bone, adenoma, neuroblastoma, cancer associated with retroviral infections, cancer associated with HPV, lung cancer, endocrine cancer, biliary tract cancer, liver cancer, pancreatic cancer, stomach cancer, bladder cancer, uterine cancer, cervical cancer, head and neck cancers, lymphocytic leukemia, myeloid leukemia, Hodgkin's lymphoma, and chronic lymphocytic leukemia.   
     
     
         13 . The method of  claim 12 , wherein the polypeptide has at least 90% identity to an IL-21 polypeptide comprising residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2. 
     
     
         14 . The method of  claim 13 , wherein the polypeptide has at least 95% identity to an IL-21 polypeptide comprising residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2. 
     
     
         15 . The method of  claim 13 , wherein the polypeptide comprises residues 41 (Gln) to 148 (Ile) of SEQ ID NO: 2 or residues 32 (Gln) to 162 (Ser) of SEQ ID NO: 2. 
     
     
         16 . The method of  claim 12 , wherein said monoclonal antibody is Rituxan. 
     
     
         17 . The method of  claim 12 , wherein said monoclonal antibody inhibits CTLA4.