Therapeutic method and composition utilizing antigen-antibody complexation and presentation by dendritic cells

Abstract

Disclosed are methods and compositions for use in immunotherapy. These methods and compositions are particularly useful for exploiting dendritic cells to present an antigen to a patient, particularly where the patient has a disease associated with the antigen. The invention provides methods for treating a patient having a disease associated with an antigen. The methods according to the invention comprise combining ex vivo an antigen and an antigen-presenting cell binding agent specific for the antigen, and administering the composition to a patient suffering from a disease associated with the antigen, wherein the patient receives a therapeutic benefit.

We claim:  
     
         1 . A method for treating a patient suffering from a disease associated with an antigen, comprising administering to the patient a composition comprising an antigen associated with the disease, a dendritic cell binding agent specific for the antigen, and a dendritic cell autologous to the patient, wherein the patient administered the composition receives a therapeutic benefit.  
     
     
         2 . The method of  claim 1 , wherein the antigen is complexed to the binding agent.  
     
     
         3 . The method of  claim 1 , wherein the dendritic cell added to the composition is an immature dendritic cell.  
     
     
         4 . The method of  claim 3 , wherein the composition is incubated ex vivo under conditions that allow for maturation of the immature dendritic cell prior to administering the composition to the patient.  
     
     
         5 . The method of  claim 1 , wherein the dendritic cell added to the composition is a dendritic cell precursor.  
     
     
         6 . The method of  claim 5 , wherein the composition is incubated ex vivo under conditions that allow for maturation of the dendritic cell precursor prior to administering the composition to the patient.  
     
     
         7 . The method of  claim 1 , wherein the patient is a human.  
     
     
         8 . The method of  claim 1 , wherein a CD8+ IFN-γ producing T cell is activated to induce a CTL immune response in the patient administered the composition.  
     
     
         9 . The method of  claim 1 , wherein a CD4+ IFN-γ producing T cell is activated to induce a helper T cell immune response in the patient administered the composition.  
     
     
         10 . The method of  claim 1 , wherein a humoral immune response is activated in the patient administered the composition.  
     
     
         11 . The method of  claim 1 , wherein the dendritic cell binding agent specifically binds to the antigen and binds to an Fcγ receptor on a dendritic cell in the patient administered with the composition, wherein the Fcγ receptor is selected from the group consisting of an Fcγ Type I (CD64) receptor, an Fcγ Type II (CD32) receptor, and an Fcγ Type I CD16 (FcγRIII) receptor  
     
     
         12 . The method of  claim 1 , wherein the dendritic cell binding agent is an antibody.  
     
     
         13 . The method of  claim 12 , wherein the dendritic cell binding agent is a xenotypic antibody to the patient.  
     
     
         14 . The method of  claim 13 , wherein the xenotypic antibody elicits a host anti-xenotypic antibody response in the patient.  
     
     
         15 . The method of  claim 13 , wherein host anti-xenotypic antibodies (HAXA) are present in the patient's blood prior to administering the composition.  
     
     
         16 . The method of  claim 13 , wherein the xenotypic antibody is a murine monoclonal antibody.  
     
     
         17 . The method of  claim 16 , wherein the murine monoclonal antibody is selected from the group consisting of Alt-1, Alt-2, Alt3, Alt-4, Alt-5; and Alt-6.  
     
     
         18 . The method of  claim 13 , wherein the composition further comprises human anti-xenotypic antibodies (HAXA).  
     
     
         19 . A therapeutic composition comprising a purified dendritic cell binding agent that is specific for an antigen associated with a disease, a dendritic cell, and the antigen associated with the disease  
     
     
         20 . The composition of  claim 19 , wherein binding of the dendritic cell binding agent to a receptor on the dendritic cell blocks binding of a natural ligand to the receptor.