Therapeutic uses of factors which inhibit or neutralize MIF activity

Abstract

The present invention relates to methods of treating disorders related to cellular overproliferation comprising neutralizing the production or activity of macrophage migration inhibitory factor (MIF). The invention also relates to therapeutic compositions comprising factors which inhibit or neutralize MIF activity, such as, MIF antisense RNA molecules and MIF monoclonal antibodies and derivatives or analogs thereof. The invention further relates to the uses of such compositions and methods for the treatment of malignancies, including, but not limited to, B and T cell lymphomas.

1 . A compound that is an agent that inhibits or neutralizes the biological activity of macrophage migration inhibitory factor (MIF). 
     
     
         2 . The compound of  claim 1  in which the agent is an antisense molecule complementary to MIF mRNA. 
     
     
         3 . The compound of  claim 1  in which the agent is a ribozyme molecule specific for MIF mRNA. 
     
     
         4 . The compound of  claim 1  in which the agent is a triple helix component. 
     
     
         5 . The compound of  claim 1  in which the agent is an anti-MIF antibody. 
     
     
         6 . A pharmaceutical composition comprising a therapeutically effective amount of an agent which inhibits or neutralizes macrophage migration inhibitory factor (MIF) and a pharmaceutically acceptable carrier. 
     
     
         7 . The composition of  claim 6  in which the agent is an antisense molecule complementary to MIF mRNA. 
     
     
         8 . The composition of  claim 6  in which the agent is a ribozyme molecule specific for MIF mRNA. 
     
     
         9 . The composition of  claim 6  in which the agent is a triple helix component. 
     
     
         10 . The composition of  claim 6  in which the agent is an anti-MIF antibody. 
     
     
         11 . A method of treating or preventing a disease or disorder which involves cell overproliferation in a subject comprising administering to a subject in which such treatment or prevention is desired a therapeutically effective amount of an agent which inhibits or neutralizes macrophage migration inhibitory factor (MIF) activity. 
     
     
         12 . The method according to  claim 11  in which the subject is a human. 
     
     
         13 . The method according to  claim 11  in which the disease or disorder is a B cell or T cell lymphoma. 
     
     
         14 . A pharmaceutical composition comprising a therapeutically effective amount of an antibody that immunospecifically binds to migration inhibitory factor (MIF) and a pharmaceutically acceptable carrier. 
     
     
         15 . A pharmaceutical composition comprising a therapeutically effective amount of a fragment or derivative of an antibody that immunospecifically binds to migration inhibitory factor (MIF), said fragment or derivative containing the binding domain of the antibody, and a pharmaceutically acceptable carrier. 
     
     
         16 . A method of treating or preventing a disease or disorder which involves cell overproliferation in a subject comprising administering to a subject in which such treatment or prevention is desired a therapeutically effective amount of an antibody that immunospecifically binds migration inhibitory factor. 
     
     
         17 . The method according to  claim 16  in which the subject is a human. 
     
     
         18 . The method according to  claim 16  in which the disease or disorder is a B cell or T cell lymphoma. 
     
     
         19 . The method according to  claim 16  in which the disease or disorder is selected from the group consisting of premalignant conditions, benign tumors, hyperproliferative disorders and benign dysproliferative disorders. 
     
     
         20 . The method according to  claim 16  in which the disease or disorder is selected from the group consisting of angiomas and diabetic retiropathy. 
     
     
         21 . (canceled) 
     
     
         22 . A method of treating or preventing tumor neovascularization in a subject comprising administering to a subject in which such treatment or prevention is desired a therapeutically effective amount of an agent which inhibits or neutralizes macrophage migration inhibitory factor (MIF) activity. 
     
     
         23 . The method of  claim 22  in which the agent is an antibody that binds to MIF. 
     
     
         24 . The method of  claim 22  in which the agent is an antisense molecule complementary to MIF mRNA. 
     
     
         25 . The method according to  claim 16  in which the disease or disorder is selected from the group consisting of esophageal cancer, stomach cancer, renal carcinoma, bladder cancer, breast cancer, colon cancer, lung cancer, melanoma, nasopharyngeal cancer, osteocarcinoma, ovarian cancer and uterine cancer.