Modulation of Regulatory T Cells by Human IL-18

Abstract

The present invention relates to compositions and methods for modulating the presence and/or activity of regulatory T cells in a subject.

1 . A method for decreasing the number of CD4 + CD25 + FoxP3 +  Tregs in a subject, said method comprising administering a therapeutically-effective amount of interleukin 18 (IL-18) to said subject, wherein said CD4 + CD25 + FoxP3 +  Tregs are selectively depleted in said subject. 
     
     
         2 . The method of  claim 1 , wherein said IL-18 is human IL-18. 
     
     
         3 . The method of  claim 1 , wherein said subject is a human subject. 
     
     
         4 . The method of  claim 3 , wherein said human subject is afflicted with at least one disorder selected from cancer, a retroviral infection or a parasitic infection. 
     
     
         5 . A method for decreasing the number of systemic Treg cells in a subject afflicted with cancer, said method comprising administering a therapeutically-effective amount of IL-18 to said subject, wherein the number of systemic Treg cells is decreased in said subject. 
     
     
         6 . A method for decreasing the number of intratumoral Treg cells in a subject afflicted with cancer, said method comprising administering a therapeutically-effective amount of IL-18 to said subject, wherein the number of intratumoral Treg cells is decreased in said subject. 
     
     
         7 . A method for increasing the number of systemic CD8 +  effector T-cells in a subject afflicted with cancer, said method comprising administering a therapeutically-effective amount of IL-18 to said subject, wherein the number of systemic CD8 +  effector T-cells is increased in said subject. 
     
     
         8 . A method for increasing the number of intratumoral CD8 +  effector T-cells in a subject afflicted with cancer, said method comprising administering a therapeutically-effective amount of IL-18 to said subject, wherein the number of intratumoral CD8 +  effector T-cells is increased in said subject. 
     
     
         9 . The method of  claim 1 , wherein said IL-18 is administered in conjunction with at least one additional therapeutic component. 
     
     
         10 . The method of  claim 9 , wherein said therapeutic component is an antibody, an antibody-toxin conjugate, a toxin, a chemotherapeutic molecule, a DNA vaccine, an antisense molecule, an siRNA molecule, a stem cell, a tumor-specific T cell, or an antigen-presenting cell. 
     
     
         11 . The method of  claim 1 , wherein said IL-18 is administered as part of an allogeneic tissue transplant. 
     
     
         12 . The method of  claim 11  wherein said tissue transplant is selected from peripheral blood mononuclear cell (PBMC) transplant or bone marrow transplant (BMT). 
     
     
         13 . The method of  claim 4 , wherein said cancer is lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, breast cancer, hematologic cancer, skin cancer, or adrenal gland cancers. 
     
     
         14 . The method of  claim 13 , wherein the cancer is lung cancer. 
     
     
         15 . A method for depleting CD4 + CD25 + FoxP3 +  Tregs in a subject, said method comprising administering a composition to said subject, wherein said composition increases the activity of IL-18 in said subject, wherein said CD4 + CD25 + FoxP3 +  Tregs are selectively depleted in said subject. 
     
     
         16 . The method of  claim 1 , wherein said IL-18 is conjugated to polyethylene glycol (PEG).