Chemokine receptor antagonists as therapeutic agents

Abstract

The present invention provides methods and compositions to reduce immune tolerance at specific sites. In one aspect, the present invention comprises methods and compositions to reduce tumorigenicity. In an embodiment, the present invention reduces recruitment of tolerance-inducing antigen presenting cells (APCs) or their precursors to a tumor and/or tumor draining lymph node by decreasing binding of at least one tumor-associated ligand to a chemokine receptor present on the tolerance-inducing APCs or APC precursors. In an embodiment, the chemokine receptor is CCR6 and the tumor-associated ligand is mip-3α. In another aspect, the present invention comprises methods and compositions to reduce immune tolerance to a virus. In an embodiment, the virus is HIV. The present invention further provides for the development of CCR6 antibodies and antagonists as therapeutic agents to prevent or reduce immune tolerance.

1 . A method to reduce recruitment of IDO+ dendritic cells that inhibit T-cell proliferation to a site of infection in a human subject comprising administering a composition comprising an antibody to CCR6 to the subject to reduce recruitment of the IDO+ dendritic cells to the site of infection, wherein the IDO+ dendritic cells express CCR6 and elevated levels of indoleamine 2,3-dioxygenase (IDO). 
     
     
         2 . The method of  claim 1 , wherein the site of infection comprises infection by human immunodeficiency virus (HIV). 
     
     
         3 . The method of  claim 1 , wherein the site of infection comprises lymphoid tissue.