Polypeptide that binds aberrant cells and induces apoptosis

Abstract

Described are proteinaceous molecules comprising at least a domain that comprises an amino acid sequence that specifically binds to an MHC-peptide complex on an aberrant cell, functionally connected with a substance that induces apoptosis in aberrant cells, but not in normal cells. These proteinaceous molecules are preferably used in selectively modulating biological processes. The provided proteinaceous molecules are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers.

1 .- 21 . (canceled) 
     
     
         22 . A molecule comprising:
 at least one domain that comprises an amino acid sequence that specifically binds to an MHC-peptide complex, wherein the peptide within the MHC-peptide complex comprises a MAGE peptide, said at least one domain functionally connected with   a substance that induces apoptosis in aberrant cells, but not normal cells.   
     
     
         23 . The molecule of  claim 22 , wherein the substance is an apoptosis-inducing polypeptide or protein and the at least one domain are linked via peptide bonds. 
     
     
         24 . The molecule of  claim 23 , which comprises a single polypeptide chain. 
     
     
         25 . The molecule of  claim 22 , wherein the at least one domain specifically binds an MHC-1-peptide complex. 
     
     
         26 . The molecule of  claim 22 , wherein the substance is apoptin or a fragment and/or derivative thereof able to induce apoptosis in an aberrant cells, but not in a normal cell. 
     
     
         27 . The molecule of  claim 22 , wherein the substance comprises a statin. 
     
     
         28 . The molecule of  claim 22 , wherein the at least one domain is linked to the substance through a non-peptide bond. 
     
     
         29 . A polynucleotide encoding a domain that comprises an amino acid sequence that specifically binds to an MHC-peptide complex. 
     
     
         30 . A polynucleotide encoding the molecule of  claim 23 . 
     
     
         31 . A vector comprising the polynucleotide of  claim 30  together with elements for expression in a suitable host cell. 
     
     
         32 . A host cell comprising the polynucleotide of  claim 29  integrated into the host cell. 
     
     
         33 . A method for producing a molecule, the method comprising:
 culturing the host cell of  claim 32 ,   expressing the polynucleotide, and   harvesting the resulting molecule.   
     
     
         34 . A pharmaceutical composition comprising:
 the polypeptide of  claim 22 , and   a suitable diluent and/or excipient.   
     
     
         35 . The pharmaceutical composition of  claim 34 , further comprising:
 a conventional cytostatic and/or tumoricidal agent.   
     
     
         36 . A method of treating a subject for cancer, the method comprising:
 utilizing the molecule of  claim 22  in the treatment of the subject's cancer.   
     
     
         37 . The method according to  claim 36 , wherein the molecule is utilized as an adjuvant treatment of the cancer. 
     
     
         38 . The method according to  claim 36 , wherein the molecule is utilized in a combination chemotherapy treatment of cancer. 
     
     
         39 . A method of treating a subject for cancer, the method comprising:
 administering the pharmaceutical composition of  claim 34  to the subject so as to treat the cancer.