Antibody and chemokine constructs and their use in the treatment of infections of immunological diseases

Abstract

The invention is directed to chimeric polypeptides, e.g., bispecific antibodies, comprising a chemokine receptor binding domain and a T cell surface polypeptide or cell toxin binding domain, nucleic acids that encode them, and methods of making and using them. The chimeric polypeptides of the invention can include, be bound to, or attached to, a cell toxin. The invention is also directed to pharmaceutical compositions and methods for making and using them, including the treatment of immunological disorders, such as autoimmune diseases, and for the targeted elimination of cells, e.g., T lymphocytes and other cells latently infected with a primate immunodeficiency virus, such as a human immunodeficiency virus, e.g., HIV-1.

1 . A chimeric polypeptide comprising 
 a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and,    a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         2 . The chimeric polypeptide of  claim 1 , wherein the chemokine receptor is a chemokine receptor 5 (CCR5).  
     
     
         3 . The chimeric polypeptide of  claim 2 , wherein the chemokine receptor 5 (CCR5) is a human chemokine receptor 5 (CCR5).  
     
     
         4 . The chimeric polypeptide of  claim 2 , wherein the moiety that specifically binds to the chemokine receptor comprises a RANTES or a fragment thereof capable of binding to the CCR5 receptor.  
     
     
         5 . The chimeric polypeptide of  claim 2 , wherein the moiety that specifically binds to the CCR5 chemokine receptor comprises a MIP-1α or a fragment thereof capable of binding to the CCR5 receptor.  
     
     
         6 . The chimeric polypeptide of  claim 2 , wherein the moiety that specifically binds to the CCR5 chemokine receptor comprises MIP-1β, MCP-2, or MCP-3 or a fragment thereof capable of binding to the CCR5 receptor.  
     
     
         7 . The chimeric polypeptide of  claim 1 , wherein the moiety that specifically binds to the chemokine receptor comprises an IP-10 (CXCL10), a MIG (CXCL9), an I-TAC (CXCL11) or a fragment thereof capable of binding to the CXCR3 chemokine receptor.  
     
     
         8 . The chimeric polypeptide of  claim 1 , wherein the chemokine receptor is a CXCR3.  
     
     
         9 . The chimeric polypeptide of  claim 1 , wherein the chemokine receptor is a CCR4.  
     
     
         10 . The chimeric polypeptide of  claim 1 , wherein the chemokine receptor is a CCR6 .  
     
     
         11 . The chimeric polypeptide of  claim 1 , wherein the chemokine receptor is a CCR10.  
     
     
         12 . The chimeric polypeptide of  claim 1 , wherein the chemokine receptor is a CXCR4, CCR1, CCR2, CCR3, CCR7, CCR8, CCR9, XCR1, or a CX3CR1.  
     
     
         13 . The chimeric polypeptide of  claim 1 , wherein the T cell surface polypeptide comprises a CD3 polypeptide.  
     
     
         14 . The chimeric polypeptide of  claim 1 , wherein the cell toxin comprises a  Pseudomonas  exotoxin.  
     
     
         15 . The chimeric polypeptide of  claim 14 , wherein the  Pseudomonas  exotoxin comprises a PE38 exotoxin, a PE40 exotoxin or a PE37 exotoxin.  
     
     
         16 . The chimeric polypeptide of  claim 1 , wherein the cell toxin comprises a diptheria toxin.  
     
     
         17 . The chimeric polypeptide of  claim 1 , wherein the cell toxin is cross-linked to the chimeric polypeptide.  
     
     
         18 . The chimeric polypeptide of  claim 1 , wherein polypeptide comprises a recombinant fusion protein.  
     
     
         19 . The chimeric polypeptide of  claim 1 , wherein the moiety that specifically binds to a chemokine receptor comprises an antigen binding domain derived from an antibody that specifically binds to the chemokine receptor.  
     
     
         20 . The chimeric polypeptide of  claim 1 , wherein the moiety that specifically binds to a T cell surface polypeptide comprises an antigen binding domain derived from an antibody that specifically binds to the T cell surface polypeptide.  
     
     
         21 . The chimeric polypeptide of  claim 1 , wherein the moiety that specifically binds to a cell toxin comprises an antigen binding domain derived from an antibody that specifically binds to the cell toxin.  
     
     
         22 . A recombinant fusion protein comprising 
 a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and,    a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         23 . A bispecific antibody comprising 
 a first antigen binding domain that specifically binds to a chemokine receptor; and,    a second antigen binding domain that specifically binds to a T cell surface polypeptide, a cell toxin, or a third antigen binding domain that specifically binds to or is linked to a T cell surface polypeptide or a comprising cell toxin.    
     
     
         24 . (canceled)  
     
     
         25 . The bispecific antibody of  claim 23 , wherein the bispecific antibody is a single chain antibody construct.  
     
     
         26 . The bispecific antibody of  claim 23 , wherein the single chain antibody construct comprises a V L  and a V H  domain capable of specifically binding the chemokine receptor and a V H  and a V L  domain capable of specifically binding a T cell surface polypeptide.  
     
     
         27 . The bispecific antibody of  claim 23 , wherein the antigen binding domain that specifically binds to a chemokine receptor comprises a murine anti-human CCR5 antibody MC-1.  
     
     
         28 . The bispecific antibody of  claim 27 , comprising V L  and V H  domains arranged in the order V L (MC-1)-V H (MC-1)-V H (CD3)-V L (CD3).  
     
     
         29 . The bispecific antibody of  claim 27 , wherein the V L (MC-1) domain comprises an amino acid sequence as set forth in SEQ ID NO:12.  
     
     
         30 . The bispecific antibody of  claim 27 , wherein the V H (MC-1) domain comprises an amino acid sequence as set forth in SEQ ID NO:16.  
     
     
         31 . The bispecific antibody of  claim 27 , wherein the V H (CD3) domain comprises an amino acid sequence as set forth in SEQ ID NO:26.  
     
     
         32 . The bispecific antibody of  claim 27 , wherein the V L (CD3) domain comprises an amino acid sequence as set forth in SEQ ID NO: 28.  
     
     
         33 . (canceled)  
     
     
         34 . The bispecific antibody of  claim 23 , wherein the second antigen binding domain specifically binds to a cell toxin.  
     
     
         35 . The bispecific antibody of  claim 23 , wherein the antibody is covalently bound to a cell toxin.  
     
     
         36 . The bispecific antibody of  claim 23 , wherein the antibody is bound to a second antibody that binds to a CD3 antigen or a cell toxin.  
     
     
         37 . A nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.  
     
     
         38 . A vector comprising a nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.  
     
     
         39 . A transformed cell comprising a nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.  
     
     
         40 . A pharmaceutical composition comprising a chimeric polypeptide, a nucleic, a vector, or a transformed cell; and, a pharmaceutically acceptable excipient; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the vector comprises a nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the transformed cell comprises a nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         41 . A kit comprising a chimeric polypeptide, a nucleic acid, a vector, a transformed cell; or a pharmaceutical composition comprising the chimeric polypeptide, the vector or the cell; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the vector comprises a nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the transformed cell comprises a nucleic acid encoding a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         42 . Use of a chimeric polypeptide to prepare a pharmaceutical composition for the elimination of cells that are latently infected with a primate immunodeficiency virus; wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.  
     
     
         43 . Use of a chimeric nucleic acid to prepare a pharmaceutical composition for the elimination of cells that are latently infected with a primate immunodeficiency virus, wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.  
     
     
         44 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of an inflammatory renal disease; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         45 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of an allergic reaction; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         46 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of an inflammatory bowel disease; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         47 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of multiple sclerosis; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         48 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of a skin disease; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         49 . The use of  claim 48 , wherein the skin disease is skin inflammation, atopic dermatitis or psoriasis.  
     
     
         50 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of diabetes; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         51 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of a transplant rejection; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         52 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of an inflammatory joint disease; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         53 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of a graft versus host disease; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         54 . Use of a chimeric polypeptide or a chimeric nucleic acid to prepare a pharmaceutical composition for the treatment of an autoimmune disease; 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         55 . The use of  claim 54 , wherein the autoimmune disease is type I diabetes or rheumatoid arthritis.  
     
     
         56 . A method for eliminating a cell infected with a primate immunodeficiency virus comprising administering a composition comprising a chimeric polypeptide or a nucleic acid, in amounts sufficient to kill the cell. 
 wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin.    
     
     
         57 . The method of  claim 56 , wherein the primate immunodeficiency virus is a human immunodeficiency virus.  
     
     
         58 . The method of  claim 57 , wherein the human immunodeficiency virus is HIV-1.  
     
     
         59 . The method of  claim 56 , wherein the cell is latently infected with a primate immunodeficiency virus.  
     
     
         60 . A method for the treatment of a primate immunodeficiency virus comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the primate immunodeficiency virus.    
     
     
         61 . The method of  claim 60 , wherein the treatment further comprises administration of drugs employed in HAART.  
     
     
         62 . A method for the treatment of an inflammatory renal disease comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the inflammatory renal disease.    
     
     
         63 . A method for the treatment of an allergic reaction comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the allergic reaction.    
     
     
         64 . A method for the treatment of an inflammatory bowel disease comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the inflammatory bowel disease.    
     
     
         65 . A method for the treatment of multiple sclerosis comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the multiple sclerosis.    
     
     
         66 . A method for the treatment of a skin disease comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the skin disease.    
     
     
         67 . The method of  claim 66 , wherein the skin disease is skin inflammation, atopic dermatitis or psoriasis.  
     
     
         68 . A method for the treatment of diabetes comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the diabetes.    
     
     
         69 . A method for the treatment of a transplant rejection comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the transplant rejection.    
     
     
         70 . A method for the treatment of inflammatory joint disease comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the inflammatory joint disease.    
     
     
         71 . The method of  claim 70 , wherein the inflammatory joint disease comprises arthritis.  
     
     
         72 . A method for the treatment of a graft versus host disease comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the transplant rejection.    
     
     
         73 . A method for the treatment of an autoimmune disease comprising the following steps: 
 (a) providing a pharmaceutical composition comprising a chimeric polypeptide or a nucleic acid,    wherein the chimeric polypeptide comprises a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin,    wherein the nucleic acid encodes a chimeric polypeptide comprising a first polypeptide domain comprising at least one moiety that specifically binds to a chemokine receptor; and, a second polypeptide domain comprising at least one moiety that specifically binds to a T cell surface polypeptide or a cell toxin, or, comprising a cell toxin; and    (b) administering the pharmaceutical composition in amounts sufficient to treat the transplant rejection.    
     
     
         74 . The method of  claim 73 , wherein the autoimmune disease is type I diabetes or rheumatoid arthritis.  
     
     
         75 . A method of making a chimeric composition that can bind to a chemokine receptor and a cell toxin comprising the following steps: 
 (a) providing a first polypeptide comprising at least one moiety that specifically binds to a chemokine receptor and at least one moiety that specifically binds to a second polypeptide comprising an antigen binding domain, wherein the antigen comprises a compound comprising a cell toxin;    (b) contacting the first and second polypeptide with the compound in vivo or in vitro under conditions wherein the first polypeptide specifically binds to the second polypeptide, and the second polypeptide specifically binds to the compound, thereby making the chimeric composition.    
     
     
         76 . A method of making a chimeric composition that can bind to a chemokine receptor and a T cell surface antigen comprising the following steps: 
 (a) providing a first polypeptide comprising at least one moiety that specifically binds to a chemokine receptor and at least one moiety that specifically binds to a second polypeptide comprising an antigen binding domain, wherein the antigen comprises a compound comprising a T cell surface antigen binding domain;    (b) contacting the first polypeptide with the second polypeptide in vivo or in vitro under conditions wherein the first polypeptide specifically binds to the second polypeptide, and the second polypeptide specifically binds to the compound, thereby making a chimeric composition.    
     
     
         77 . The method of  claim 76 , wherein the T cell surface antigen comprises a CD3 antigen.  
     
     
         78 . The method of  claim 76 , wherein further comprising a cell toxin covalently bound to the chimeric composition.  
     
     
         79 . The method of  claim 76 , wherein the cell toxin is a truncated  Pseudomonas  exotoxin A (PE38).