Use of truncated cysteine IL28 and IL29 mutants to treat cancers and autoimmune disorders

Abstract

Methods for treating patients with cancer and autoimmune disorders using IL-28 and IL-29 molecules. The IL-28 and IL-29 molecules include polypeptides that have homology to the human IL-28 or IL-29 polypeptide sequence and proteins fused to a polypeptide with IL-28 and IL-29 functional activity. The molecules can be used as a monotherapy or in combination with other known cancer and/or autoimmune therapeutics.

1 . A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.  
     
     
         2 . The method of  claim 1  wherein the polypeptide further comprises polyethylene glycol.  
     
     
         3 . The method of  claim 2  wherein the polyethylene glycol is covalently linked amino-terminally to the polypeptide.  
     
     
         4 . The method of  claim 2  wherein the polyethylene glycol is about 20 kD, 30 kD, or 40 kD.  
     
     
         5 . The method of  claim 2  wherein the polyethylene glycol is linear or branched.  
     
     
         6 . The method of  claim 2  wherein the polyethylene glycol is monomethoxy-PEG propionaldehyde.  
     
     
         7 . The method of  claim 1  wherein the patient is a mammal.  
     
     
         8 . The method of  claim 7  wherein the patient is a human.  
     
     
         9 . A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.  
     
     
         10 . A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175; and    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.    
     
     
         11 . A method of treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.    
     
     
         12 . The method of  claim 11  wherein the second polypeptide is an Interferon.  
     
     
         13 . The method of  claim 12  wherein the second polypeptide is Interferon-alpha, Interferon-beta, or Interferon-gamma.  
     
     
         14 . A method of inhibiting the progressive of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.  
     
     
         15 . A method of inhibiting the progression of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.    
     
     
         16 . A method of delaying the onset of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.  
     
     
         17 . A method of delaying the onset of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.    
     
     
         18 . A method of reducing the severity of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.  
     
     
         19 . A method of reducing the severity of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.    
     
     
         20 . A method of inhibiting at least one of the conditions or symptoms of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.  
     
     
         21 . A method of inhibiting at least one of the conditions or symptoms of cancer comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of B-cell lymphomas, chronic lymphocytic leukemia, acute lymphocytic leukemia, Non-Hodgkin's lymphomas, multiple myeloma, acute myelocytic leukemia, chronic myelocytic leukemia, renal cell carcinoma, hepatocellular carcinoma, cervical cancer, melanoma, thyroid carcinoma, malignant gliomas, breast cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, stomach cancer, ovarian cancer, testicular cancer, Kaposi's sarcoma, and bone cancer.    
     
     
         22 . A method of inhibiting at least one of the conditions or symptoms of non-Hogkin's lymphoma comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the at least one of the conditions or symptoms is selected from the group of painless swelling of a lymph node in the neck, armpit or groin, night sweats, unexplained fever, weight loss, and excessive tiredness.  
     
     
         23 . A method of inhibiting at least one of the conditions or symptoms of non-Hodgkin's lymphoma comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide; and    a pharmaceutically acceptable vehicle;    wherein the at least one of the conditions or symptoms is selected from the group of painless swelling of a lymph node in the neck, armpit or groin, night sweats, unexplained fever, weight loss, and excessive tiredness.    
     
     
         24 . A method of inhibiting at least one of the conditions or symptoms of multiple myeloma comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the at least one of the conditions or symptoms is selected from the group of back pain, loss of height, anaemia, kidney damage, repeated respiratory infections, and hypercalcaemia.  
     
     
         25 . A method of inhibiting at least one of the conditions or symptoms of multiple myeloma comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide; and    a pharmaceutically acceptable vehicle;    wherein the at least one of the conditions or symptoms is selected from the group of back pain, loss of height, anaemia, kidney damage, repeated respiratory infections, and hypercalcaemia.    
     
     
         26 . A method of inhibiting at least one of the conditions or symptoms of head and neck tumours comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the at least one of the conditions or symptoms is selected from the group of an ulcer or sore area in the head or neck that does not heal within a few weeks, difficulty in swallowing, trouble with breathing or speaking, a numb feeling in the mouth, nose bleeds, persistent earache, difficulty in hearing, and swelling or lump in the mouth or neck.  
     
     
         27 . A method of inhibiting at least one of the conditions or symptoms of head and neck tumours comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide; and    a pharmaceutically acceptable vehicle;    wherein the at least one of the conditions or symptoms is selected from the group of an ulcer or sore area in the head or neck that does not heal within a few weeks, difficulty in swallowing, trouble with breathing or speaking, a numb feeling in the mouth, nose bleeds, persistent earache, difficulty in hearing, and swelling or lump in the mouth or neck.    
     
     
         28 . A method of treating an autoimmune disorder comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the autoimmune disorder is selected from the group of multiple sclerosis, arthritis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, and psoriasis.  
     
     
         29 . A method of treating an autoimmune disorder comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175, wherein the autoimmune disorder is selected from the group of multiple sclerosis, arthritis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, and psoriasis.  
     
     
         30 . A method of an autoimmune disorder comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of multiple sclerosis, arthritis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, and psoriasis.    
     
     
         31 . A method of inhibiting the progression of an autoimmune disorder comprising administering to a patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a second polypeptide;    a pharmaceutically acceptable vehicle; and    wherein the cancer is selected from the group of multiple sclerosis, arthritis, rheumatoid arthritis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, and psoriasis.    
     
     
         32 . A method of delaying a multiple sclerosis relapse in a patient comprising administering to the patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a pharmaceutically acceptable vehicle.    
     
     
         33 . A method of reducing the severity of a multiple sclerosis relapse in a patient comprising administering to the patient in need thereof a therapeutically effective amount of a formulation comprising: 
 a polypeptide having at least 95% sequence identity with a sequence selected from the group of SEQ ID NOs:163, 165, 167, 169, 171, 173 and 175;    a pharmaceutically acceptable vehicle.