Aberrant cell-restricted immunoglobulins provided with a toxic moiety

Abstract

Described are immunoglobulins provided with a toxic moiety, comprising at least an immunoglobulin variable region that specifically binds to an MHC-peptide complex preferentially associated with aberrant cells. These immunoglobulins provided with a toxic moiety may be used in selectively modulating biological processes. These immunoglobulins provided with a toxic moiety are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrations, such as cancers and autoimmune diseases.

1 . An immunoglobulin provided with a toxic moiety, comprising at least an immunoglobulin variable region that specifically binds to an MHC-peptide complex preferentially associated with aberrant cells. 
     
     
         2 . The immunoglobulin according to  claim 1  wherein said immunoglobulin variable region is a Vh or Vhh. 
     
     
         3 . The immunoglobulin according to  claim 2  wherein said immunoglobulin variable region further comprises a Vl. 
     
     
         4 . The immunoglobulin according to  claim 3 , which is a human IgG. 
     
     
         5 . The immunoglobulin of  claim 1 , wherein the MHC-peptide complex is specific for aberrant cells. 
     
     
         6 . The immunoglobulin of  claim 1 , wherein the toxic moiety is chemically linked to the immunoglobulin. 
     
     
         7 . The immunoglobulin of  claim 1 , wherein the toxic moiety is a fusion protein, fused to the immunoglobulin at the DNA level. 
     
     
         8 . A pharmaceutical composition comprising:
 the immunoglobulin of  claim 1 , and   suitable diluents and/or excipients.   
     
     
         9 . A method of treating a host suffering from a disease associated with aberrant cells, the method comprising:
 utilizing an immunoglobulin provided with a toxic moiety of  claim 1 , for the treatment of the host suffering from a disease associated with aberrant cells.   
     
     
         10 . The method according to  claim 9 , wherein the toxic moiety is internalized into the aberrant cell. 
     
     
         11 . A method of treating a subject determined to be suffering from cancer, the method comprising:
 utilizing the immunoglobulin of  claim 1  to treat cancer.   
     
     
         12 . The method according to  claim 11 , wherein at least the toxic moiety is internalized into an aberrant cell of the subject. 
     
     
         13 . An immunoglobulin provided with a toxic moiety according to  FIG. 5B . 
     
     
         14 . The immunoglobulin of  claim 5 , wherein the MHC-peptide complex is specific for aberrant cells through a peptide derived from MAGE. 
     
     
         15 . The immunoglobulin of  claim 14 , wherein the MAGE is MAGE-A. 
     
     
         16 . The immunoglobulin of  claim 7 , wherein the toxic moiety is a fusion protein fused to the immunoglobulin at the DNA level through a linking sequence. 
     
     
         17 . An immunoglobulin chemically linked with a toxic moiety comprising:
 at least a Vh or Vhh immunoglobulin variable region that specifically binds to an MHC-peptide complex, which is derived from MAGE, preferentially associated with aberrant cells,   wherein the immunoglobulin is a human IgG.   
     
     
         18 . The immunoglobulin of  claim 17  wherein the immunoglobulin variable region is a Vl. 
     
     
         19 . The immunoglobulin of  claim 17 , wherein the MAGE is MAGE-A. 
     
     
         20 . The immunoglobulin of  claim 1 , wherein the toxic moiety is a fusion protein fused to the immunoglobulin at the DNA level through a linking sequence.