Human cd3-specific antibody with immunosuppressive properties

Abstract

Described are mono- and multivalent scFv-antibodies comprising the binding sites specific for human T cell marker CD 3 . These antibodies are strongly immunosuppressive and do not cause a significant release of cytokines. Furthermore, polynucleotides encoding said antibodies are described as well as vectors comprising said polynucleotides, host cells transformed therewith and their use in the production of said antibodies. Pharmaceutical compositions containing any of the above mentioned polynucleotides, antibodies or vectors are useful for immunotherapy, preferably against acute transplant rejections.

1 . A bivalent or multivalent antibody characterized by the following features: 
 (a) it is capable of supressing an immune reaction;    (b) it is devoid of constant antibody regions; and    (c) it binds an epitope on the CD3 complex of the T-cell receptor.    
     
     
         2 . The antibody of  claim 1  that is a diabody.  
     
     
         3 . The antibody of  claim 1  that comprises two scFv antibodies linked by a peptide linker.  
     
     
         4 . The antibody of  claim 1  that is a single chain diabody.  
     
     
         5 . The antibody according to  claim 1 , wherein variable V H  and V L  domains are connected via the peptide linker SAKTTP or SAKTTPKLGG.  
     
     
         6 . The antibody according to  claim 1 , wherein its variable domains correspond to the variable domains of an antibody produced by the hybridoma of ATCC deposit number CRL 8001.  
     
     
         7 . The antibody according to  claim 6 , wherein a cysteine at position H100A has been exchanged for another amino acid.  
     
     
         8 . The antibody according to  claim 7 , wherein the cysteine has been exchanged for a serine.  
     
     
         9 . A polynucleotide, which encodes an antibody according to  claim 1 .  
     
     
         10 . An expression vector comprising the polynucleotide of  claim 9 .  
     
     
         11 . The expression vector of  claim 10 , which is pSKK3-scFv — 6-anti-CD3 (DSM 15137).  
     
     
         12 . A host cell containing the expression vector of  claim 10  or  11 .  
     
     
         13 . A pharmaceutical composition comprising the antibody of  claim 1 , the polynucleotide of  claim 9 , or the expression vector of  claim 10 .  
     
     
         14 . A method for immunotherapy comprising the step of administering to a subject the pharmaceutical composition according to  claim 13 .  
     
     
         15 . A method for immunotherapy comprising the step of administering to a subject a pharmaceutical composition comprising the antibody of  claim 1 .  
     
     
         16 . The method according to  claim 14  , wherein said immunotherapy is a therapy against acute transplant rejections.  
     
     
         17 . A method for gene therapy comprising the step of administering to a subject a pharmaceutical composition comprising the polynucleotide of  claim 9  or the expression vector of  claim 10.