Methods and compositions for reducing immune response

Abstract

The present invention provides an apparatus and method to diminish the pre-existing immune response to the administration of a therapeutic virus by the selective elimination of antiviral antibodies from the serum. The present invention provides a chromatographic material for the elimination of such antibodies. The invention further provides plasmapheresis apparatus comprising this material. The invention further provides methods for the employment of such apparatus as part of therapeutic treatment regiments.

We claim:  
     
         1 . A method for reducing the concentration of antiviral antibodies in a sample of plasma by contacting said isolated plasma with an immunoaffinity chromatographic material comprising an immunoaffinity material linked to a chromatographic support such that antibodies are retained on the immunoaffinity material.  
     
     
         2 . The method of  claim 1  wherein the immunoaffinity material is selected from the group consisting of Protein A, Protein G and a viral coat protein.  
     
     
         3 . The method of  claim 2  wherein the immunoaffinity material is a viral coat protein of an adenovirus selected from the group consisting of hexon, penton, protein IX, protein IIIA fiber, knob and penton base.  
     
     
         4 . The method of  claim 2  wherein the immunoaffinity material is protein A.  
     
     
         5 . The method of  claim 2  wherein the immunoaffinity material is protein G.  
     
     
         6 . A method of reducing the concentration of antiviral antibodies in a mammalian organism, said method comprising the steps of: 
 a) obtaining a sample of blood from said mammalian organism;    b) isolating the plasma from the cellular components from said blood sample;    c) contacting said isolated plasma with an immunoaffinity chromatographic material comprising an immunoaffinity material linked to a chromatographic support such that antibodies are retained on the immunoaffinity material;    d) reintroducing the cellular components isolated from step (b) and the purified plasma from step (c) to the mammal.    
     
     
         7 . The method of  claim 6  wherein the immunoaffinity material is selected from the group consisting of Protein A, Protein G and a viral coat protein.  
     
     
         8 . The method of  claim 7  wherein the immunoaffinity material is a viral coat protein of an adenovirus selected from the group consisting of hexon, penton, protein IX, protein IIIA fiber, knob and penton base.  
     
     
         9 . The method of  claim 8  wherein the immunoaffinity material is protein A.  
     
     
         10 . The method of  claim 8  wherein the immunoaffinity material is protein G.  
     
     
         11 . An improved method of treating a mammal with a therapeutic virus, the improvement comprising reducing the concentration of antiviral antibodies in said mammal prior to or in conjunction with the administration of said therapeutic virus by: 
 a) obtaining a sample of blood from said mammalian organism;    b) isolating the plasma from the cellular components from said blood sample;    c) contacting said isolated plasma with an immunoaffinity chromatographic material comprising an immunoaffinity material linked to a chromatographic support such that antibodies are retained on the immunoaffinity material;    d) reintroducing the cellular components isolated from step (b) and the purified plasma from step (c) to the mammal.    
     
     
         12 . The method of  claim 11  wherein the therapeutic virus is an adenovirus.  
     
     
         13 . The method of  claim 12  wherein the immunoadsorbent material is selected from the group consisting of Protein A, Protein G and a SAVID material.  
     
     
         14 . The method of  claim 13  wherein the adenovirus is a replication deficient adenovirus.  
     
     
         15 . The method of  claim 14  wherein the virus is expresses the p53 tumor suppressor gene.  
     
     
         16 . The method of  claim 5  wherein the virus is A/C/N/53.  
     
     
         17 . The method of  claim 12  wherein the adenovirus is a replication competent adenovirus.  
     
     
         18 . The method of  claim 17  wherein said replication competent virus is a conditionally replicating adenovirus.  
     
     
         19 . The method of  claim 18  wherein said conditionally replicating virus comprises a tumor specific promoter driving expression of a early adenovirus gene.  
     
     
         20 . The method of  claim 19  wherein said tumor specific promoter is the prostate specific antigen promoter.  
     
     
         21 . The method of  claim 17  wherein said replication competent adenovirus contains a deletion of in the E1b-55K gene so as to disrupt the ability of the E1B-55K gene product to bind to p53.  
     
     
         22 . The method of  claim 21  wherein said virus is dl1520.  
     
     
         23 . A composition of matter comprising SAVID immunoaffinity chromatographic material.