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 are preferably used in selectively modulating biological processes. The provided immunoglobulins provided with a toxic moiety are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers and autoimmune diseases.

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