Chimeric anti-ricin antibody

Abstract

A chimeric monoclonal antibody targeted to ricin is presented. The light chain and heavy chain constant regions are respectively made up of the light chain and heavy chain constant regions of human immunoglobulin, and the light chain and heavy chain variable regions respectively include the light chain and heavy chain variable regions of macaque immunoglobulin. The antibody does not substantially induce any immune response against chimeric antibodies.

1 . A chimeric anti-ricin monoclonal antibody, wherein:
 the constant region of the light chain essentially comprises the constant region of the light chain of a human immunoglobulin;   the constant region of the heavy chain essentially comprises the constant region of the heavy chain of a human immunoglobulin;   the variable region of the light chain comprises the variable region of the light chain of a macaque immunoglobulin;   the variable region of the heavy chain comprises the variable region of the heavy chain of a macaque immunoglobulin; and   the monoclonal antibody does not substantially induce an immune response against chimeric antibodies.   
     
     
         2 . The antibody according to  claim 1 , wherein the antibody is capable of neutralizing ricin. 
     
     
         3 . The antibody according to  claim 1 , wherein the antibody is capable of neutralizing ricin and has a ricin neutralization rate that is higher than the neutralization rate of a fragment of scFv targeted at ricin. 
     
     
         4 . The antibody according to  claim 1 , wherein:
 the constant region of the light chain comprises the constant region of the light chain of a kappa type human immunoglobulin; and   the constant region of the heavy chain comprises the constant region of the heavy chain of a type IgG1 human immunoglobulin.   
     
     
         5 . The antibody according to  claim 4 , wherein the constant region of the light chain and the constant region of the heavy chain are obtained by immunization with a Rhesus D antigen. 
     
     
         6 . The antibody according to  claim 4 , wherein the constant region of the light chain and the constant region of the heavy chain are obtained from the T125-A2 clone. 
     
     
         7 . A Fab or F(ab)′2 fragment of the monoclonal antibody according to  claim 1 . 
     
     
         8 . Nucleic acid coding for the light chain of the monoclonal antibody according to  claim 1 . 
     
     
         9 . The nucleic acid according to  claim 8 , comprising SEQ ID NO: 1, 5, 9 or 13. 
     
     
         10 . Nucleic acid coding for the heavy chain of the monoclonal antibody according to  claim 1 . 
     
     
         11 . The nucleic acid according to  claim 8 , comprising SEQ ID NO: 3, 7, 11 or 15. 
     
     
         12 . Nucleic acid coding for the light chain and coding for the heavy chain of the monoclonal antibody according to  claim 1 . 
     
     
         13 . An expression vector, comprising nucleic acid coding for the light chain, coding for the heavy chain, or coding for the light chain and the heavy chain of the monoclonal antibody according to  claim 1 , said nucleic acid being under control of elements that permit expression of the nucleic acid. 
     
     
         14 . A pharmaceutical composition, comprising at least one of:
 the monoclonal antibody according to  claim 1 ;   a Fab or F(ab)′2 fragment of said monoclonal antibody;   a nucleic acid coding for the light chain of said monoclonal antibody, coding for the heavy chain of said monoclonal antibody, or coding for the light chain and the heavy chain of said monoclonal antibody; or   a vector comprising said nucleic acid,   in association with a pharmaceutically acceptable vehicle.   
     
     
         15 . A pharmaceutical composition, comprising at least one monoclonal antibody according to  claim 1 , in association with a pharmaceutically acceptable vehicle. 
     
     
         16 . A method for treating or preventing a pathology associated with ricin contamination in a subject, comprising administering to the subject at least one of:
 the monoclonal antibody according to  claim 1 ;   a Fab or F(ab)′2 fragment of said monoclonal antibody;   a nucleic acid coding for the light chain of said monoclonal antibody, coding for the heavy chain of said monoclonal antibody, or coding for the light chain and the heavy chain of said monoclonal antibody;   a vector comprising said nucleic acid; or   a cell comprising said monoclonal antibody, said fragment, said nucleic acid, or said vector.   
     
     
         17 . A method of measuring ricin in vitro, in a biological sample from an individual who may have been contaminated by ricin, the method comprising:
 bringing the sample into contact with at least one monoclonal antibody according to  claim 1 ; and   determining the presence or absence of ricin in said sample by detecting the formation of an immune complex between the ricin and said monoclonal antibody.   
     
     
         18 . A process for decontaminating in vitro, a sample that may have been contaminated by ricin, the process comprising:
 bringing the sample into contact with at least one monoclonal antibody according to  claim 1 , and   removing from said sample any immune complexes formed between the ricin and said monoclonal antibody.   
     
     
         19 . A process for preparing the antibody according to  claim 1 , comprising:
 transforming a cell with a vector comprising a nucleic acid coding for the light chain of said monoclonal antibody, coding for the heavy chain of said monoclonal antibody, or coding for the light chain of said monoclonal antibody and the heavy chain of said monoclonal antibody;   selecting the transformed cells; and   assessing the production of said antibody from the selected cells, by determining the presence or absence of the formation of an immune complex between ricin and said monoclonal antibody.   
     
     
         20 . The process according to  claim 19 , wherein the cell is of the cell line YB2/0.