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.

We claim:  
     
         1 . A method of treating Non-Hodgkins lymphoma comprising administering to a subject in need thereof a therapeutically effective amount of a polypeptide having a functional activity of IL-21.  
     
     
         2 . The method according to  claim 1 , wherein the polypeptide has been shown to not cause proliferation of isolated cancer cells prior to administration to the subject.  
     
     
         3 . A method of treating cancer comprising administering to subject a therapeutically effective amount of a polypeptide having a functional activity of IL-21, wherein the cancer is selected from the group of renal cell carcinoma, epithelial carcinoma, breast cancer, prostate cancer, ovarian cancer and colon cancer.  
     
     
         4 . A method of treating cancer comprising administering to a subject a therapeutically effective amount of a polypeptide having a functional activity of IL-21, wherein the cancer is selected from the group of Non-Hodgkins lymphoma, renal cell carcinoma, breast cancer, prostate cancer, ovarian cancer and colon cancer and wherein there is a tumor response.  
     
     
         5 . A method of treating cancer comprising administering to a subject a therapeutically effective amount of a polypeptide having a functional activity of IL-21, wherein the cancer is selected from the group of Non-Hodgkins lymphoma, renal cell carcinoma, breast cancer, prostate cancer, ovarian cancer and colon cancer and wherein a tumor response is measured as complete response, partial response or reduction in time to progression.  
     
     
         6 . The method according to claims  1 ,  2 ,  3 ,  4 , or  5 , 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.  
     
     
         7 . The method according to claims  1 ,  2 ,  3 ,  4 , or  5 , 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.  
     
     
         8 . The method according to claims  1 ,  2 ,  3 ,  4 , or  5 , 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.  
     
     
         9 . The method according to claims  1 ,  2 ,  3 ,  4 , or  5 , wherein the polypeptide is 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.  
     
     
         10 . A method of treating Non-Hodgkins lymphoma comprising administering to a subject in need thereof a therapeutically effective amount of a fusion protein comprising a first polypeptide having a functional activity of IL-21 and a second polypeptide.  
     
     
         11 . The method according to  claim 10 , wherein the polypeptide has been shown not to cause proliferation of isolated cancer cells prior to administration to the subject.  
     
     
         12 . A method of treating cancer comprising administering to subject a therapeutically effective amount of a fusion protein comprising a first polypeptide having a functional activity of IL-21 and second polypeptide, wherein the cancer is selected from the group of renal cell carcinoma, epithelial carcinoma, breast cancer, prostate cancer, ovarian cancer and colon cancer.  
     
     
         13 . A method of treating cancer comprising administering to a subject a therapeutically effective amount of a fusion protein comprising a first polypeptide having a functional activity of IL-21 and second polypeptide, wherein the cancer is selected from the group of Non-Hodgkins lymphoma, renal cell carcinoma, breast cancer, prostate cancer, ovarian cancer and colon cancer and wherein there is a tumor response.  
     
     
         14 . A method of treating cancer comprising administering to a subject a therapeutically effective amount of a fusion protein comprising a first polypeptide having a functional activity of IL-21 and second polypeptide, wherein the cancer is selected from the group of Non-Hodgkins lymphoma, renal cell carcinoma, breast cancer, prostate cancer, ovarian cancer and colon cancer and wherein a tumor response is measured as complete response, partial response or reduction in time to progression.  
     
     
         15 . The method according to claims  10 ,  11 ,  12 ,  13 , or  14 , wherein the first 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.  
     
     
         16 . The method according to claims  10 ,  11 ,  12 ,  13 , or  14 , wherein the first 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.  
     
     
         17 . The method according to claims  10 ,  11 ,  12 ,  13 , or  14 , wherein the first 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.  
     
     
         18 . The method according to claims  10   11 ,  12 ,  13 , or  14 , wherein the first polypeptide is 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.