Method for enhancing immune responses in mammals

Abstract

The present invention provides a method for enhancing an immune response in a mammal to facilitate the elimination of a chronic pathology. The method involves the removal of immune system inhibitors from the circulation of the mammal, thus, enabling a more vigorous immune response to the pathogenic agent. The removal of immune system inhibitors is accomplished by contacting biological fluids of a mammal with one or more binding partner(s) capable of binding to and, thus, depleting the targeted immune system inhibitor(s) from the biological fluids. Particularly useful in the invention is an absorbent matrix composed of an inert, biocompatible substrate joined covalently to a binding partner, such as an antibody, capable of specifically binding to the targeted immune system inhibitor.

1 - 49 . (canceled) 
   
   
       50 . An extracorporeal system for reducing the amount of a targeted immune system inhibitor in blood, comprising:
 a) an absorbent matrix comprising an inert medium attached to at least one binding partner capable of specifically binding to a targeted immune system inhibitor; and   b) a conduit for conducting the blood to the absorbent matrix to produce altered blood having a reduced amount of the targeted immune system inhibitor,   wherein all of said binding partners in said extracorporeal system are selected from the group consisting of binding partners to: soluble receptors for tumor necrosis factor α and β, interleukin-1 receptor antagonist, soluble receptors for interleukin-1, and soluble receptors for interleukin-6.   
   
   
       51 . The extracorporeal system of  claim 50 , wherein the targeted immune system inhibitor is present in a plasma component of the blood or fraction thereof. 
   
   
       52 . The extracorporeal system of  claim 50 , wherein the inert medium is selected from the group consisting of: a hollow fiber, a macroporous bead, a cellulose-based fiber, a synthetic fiber, a flat membrane, a pleated membrane, and a silica-based particle. 
   
   
       53 . The extracorporeal system of  claim 50 , wherein the binding partner is covalently joined to the inert medium. 
   
   
       54 . The extracorporeal system of  claim 50 , wherein the binding partner is a binding partner to which the targeted immune system inhibitor binds to in nature, or a fragment of the binding partner to which the targeted immune system inhibitor binds to in nature, wherein the fragment specifically binds to the targeted immune system inhibitor. 
   
   
       55 . The extracorporeal system of  claim 50 , wherein the binding partner or fragment is produced recombinantly. 
   
   
       56 . The extracorporeal system of  claim 50 , wherein the binding partner is a monoclonal antibody or a fragment of a monoclonal antibody that specifically binds to the targeted immune system inhibitor. 
   
   
       57 . The extracorporeal system of  claim 50 , wherein the binding partner comprises a plurality of different monoclonal antibodies or fragments thereof, wherein the plurality of monoclonal antibodies or fragments thereof are capable of specifically binding to the targeted immune system inhibitor. 
   
   
       58 . The extracorporeal system of  claim 50 , wherein a plurality of binding partners are collectively capable of specifically binding to a plurality of targeted immune system inhibitors. 
   
   
       59 . The extracorporeal system of  claim 50 , wherein the binding partner comprises a polyclonal antibody preparation or fragments of a polyclonal antibody preparation that specifically bind to the targeted immune system inhibitor. 
   
   
       60 . The extracorporeal system of  claim 50 , wherein the binding partner comprises a plurality of different polyclonal antibody preparations or fragments thereof, wherein the polyclonal antibodies or fragments thereof are capable of specifically binding to the targeted immune system inhibitor. 
   
   
       61 . The extracorporeal system of  claim 50 , wherein the binding partner comprises at least one synthetic peptide. 
   
   
       62 . The extracorporeal system of  claim 61 , wherein the at least one synthetic peptide is conjugated to a carrier. 
   
   
       63 . The extracorporeal system of  claim 50 , wherein the binding partner comprises a plurality of synthetic peptides capable of specifically binding to a plurality of targeted immune system inhibitors. 
   
   
       64 . An extracorporeal system for reducing the amount of a targeted immune system inhibitor in whole blood, comprising:
 a) a means for separating whole blood into a cellular component and an acellular component or fraction of the acellular component, wherein the acellular component or the fraction of the acellular component contains a targeted immune system inhibitor;   b) a means for providing a binding partner capable of specifically binding to the targeted immune system inhibitor in (a);   c) a means for conducting the acellular component or fraction of the acellular component to the means for providing the targeted immune system inhibitor to produce an altered acellular component or fraction of the acellular component;   d) a means for conducting the altered acellular component or fraction of the acellular component from the absorbent matrix to the cellular component to produce an altered whole bloods   wherein all of said binding partners in said extracorporeal system are selected from the group consisting of binding partners to: soluble receptors for tumor necrosis factor α and β, interleukin-1 receptor antagonist, soluble receptors for interleukin-1, and soluble receptors for interleukin-6.   
   
   
       65 . An extracorporeal system for reducing the amount of a targeted immune system inhibitor in whole blood, comprising:
 a) a means for separating whole blood into a cellular component and an acellular component or fraction of the acellular component, wherein the acellular component or the fraction of the acellular component contains a targeted immune system;   b) a means for providing a binding partner capable of specifically binding to the targeted immune system inhibitor in (a);   c) a means for conducting the acellular component or fraction of the acellular component to the means for providing the targeted immune system inhibitor to produce an altered acellular component or fraction of the acellular component;   d) a means for conducting the altered acellular component or fraction of the acellular component from the absorbent matrix to the cellular component to produce an altered whole blood, wherein the means for providing a binding partner comprises an absorbent matrix comprising an inert medium attached to a binding partner capable of specifically binding to the targeted immune system inhibitor,   wherein all of said binding partners in said extracorporeal system are selected from the group consisting of binding partners to: soluble receptors for tumor necrosis factor α and β, interleukin-1 receptor antagonist, soluble receptors for interleukin-1, and soluble receptors for interleukin-6.   
   
   
       66 . The extracorporeal system of  claim 50 , further comprising an apparatus for separating whole blood into a cellular component and an acellular component or a fraction of the acellular component. 
   
   
       67 . The extracorporeal system of  claim 66 , wherein the acellular component or the fraction of the acellular component contains the targeted immune system inhibitor. 
   
   
       68 . The extracorporeal system of  claim 67 , wherein the conduit conducts the acellular component or fraction of the acellular component to the absorbent matrix to produce an altered acellular component or altered fraction of the acellular component having a reduced amount of the targeted immune system inhibitor. 
   
   
       69 . The extracorporeal system of  claim 68 , further comprising a conduit for conducting the altered acellular component or fraction of the acellular component from the absorbent matrix to the cellular component to produce an altered whole blood.