SPECIFIC BINDING AGENTS FOR KSHV vIL-6 THAT NEUTRALIZE A BIOLOGICAL ACTIVITY

Abstract

A specific binding agent is provided, wherein the specific binding agent specifically binds Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), and the specific binding agent neutralizes an activity of vIL-6. In one embodiment, the specific binding agent is an antibody. Methods are provided for using a specific binding agent that binds vIL-6, and neutralizes a biological activity of vIL-6. Methods of treatment for a KSHV-associated disorder are also provided. Methods for diagnosing a KSHV-associated disorder are provided, as are kits that include a specific binding agent of the invention. A method is also provided for testing an agent for effectiveness in treating a KSHV-associated disorder. The method includes incubating the agent with a cell free system comprising a vIL-6 receptor component and vIL-6, and comparing the binding of vIL-6 and the receptor component in the presence of the agent to binding of vIL-6 to the receptor component in the absence of the agent. A decrease in the binding of vIL-6 to the receptor component in the presence of the agent indicates that the agent is effective for treating the KSHV-associated disorder.

1 . A method for identifying an agent as being effective for treating a Kaposi's sarcoma herpesvirus (KSHV)-associated disorder, comprising
 incubating the agent with a cell free system comprising viral interleukin (vIL)-6 and an vIL-6 receptor component;   comparing binding of vIL-6 and the vIL-6 receptor component in the presence of the agent to binding of vIL-6 to the vIL-6 receptor component in the absence of the agent,   wherein a decrease in the binding of vIL-6 to the vIL-6 receptor component in the presence of the agent indicates that the agent is effective for treating a KSHV-associated disorder.   
     
     
         2 . The method of  claim 1 , wherein the vIL-6 receptor component is gp130. 
     
     
         3 . The method of  claim 1 , wherein the agent is an antibody, a chemical compound, or an antisense molecule. 
     
     
         4 . A method for determining if an agent induces conformational changes in a viral interleukin (vIL)-6, comprising
 contacting the vIL-6 with the agent in vitro;   evaluating the ability of the vIL-6 contacted with the agent to specifically bind an IL-6 receptor; and   comparing the binding of the vIL-6 and the IL-6 receptor to a control, thereby determining whether the agent induces conformational changes in the vIL-6.   
     
     
         5 . The method of  claim 4 , wherein the agent is a monoclonal antibody. 
     
     
         6 . The method of  claim 5 , wherein the control is a vIL-6 contacted with a monoclonal antibody that binds a domain within site I in Karposi's sarcoma-associated herepesvirus interleukin-6. 
     
     
         7 . The method of  claim 5 , wherein the control is a vIL-6 contacted with a monoclonal antibody that binds the C-terminal region of the AB-loop and helix B of Karposi's sarcoma-associated herepesvirus interleukin-6. 
     
     
         8 . A method of inducing an immune response in a subject to a Kaposi's sarcoma-associated herpes virus vIL-6, comprising,
 administering to the subject a therapeutically effective amount of a C-terminal region of the AB loop and helix B of the Kaposi's sarcoma-associated herpes virus interleukin (IL)-6, thereby inducing the immune response.   
     
     
         9 . The method of  claim 8 , wherein the immune response is a B cell response. 
     
     
         10 . The method of  claim 8 , wherein the immune response is a T cell response. 
     
     
         11 . A kit for detecting the presence of Kaposi's sarcoma virus, comprising a monoclonal antibody that specifically binds Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), a humanized form thereof, or a functional fragment of the monoclonal antibody or humanized form thereof, wherein the monoclonal is produced by the hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2217, PTA-2218, PTA-2219, or PTA-2220. 
     
     
         12 . The kit of  claim 11 , wherein the monoclonal antibody that specifically binds Kaposi's sarcoma-associated herpesvirus (KSHV) interleukin-6 (vIL-6), a humanized form thereof, or a functional fragment of the monoclonal antibody or humanized form thereof is labeled. 
     
     
         13 . The kit of  claim 12 , wherein the label is a radiolabel, a fluorescent label, and calorimetric label, or a luminescent label. 
     
     
         14 . The kit of  claim 11 , wherein the functional fragment is a Fab, Fab′, (Fab′) 2 , Fv or a single chain fragment. 
     
     
         15 . The kit of  claim 11 , wherein the wherein the monoclonal is produced by the hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2217. 
     
     
         16 . The kit of  claim 11 , wherein the wherein the monoclonal is produced by the hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2218. 
     
     
         17 . The kit of  claim 11 , wherein the wherein the monoclonal is produced by the hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2219. 
     
     
         18 . The kit of  claim 11 , wherein the wherein the monoclonal is produced by the hybridoma deposited as American Type Culture Collection (ATCC) Deposit No. PTA-2220.