Cross-linking polypeptide that induces apoptosis

Abstract

Described is a polypeptide comprising at least four domains specifically binding to a certain MHC peptide complex, the domains separated by linker amino acid sequences, thereby providing each domain with the capability to bind a separate MHC peptide complex, to a nucleic acid molecule encoding such a polypeptide, to a vector comprising such a nucleic acid molecule, to a host cell for expression of such a polypeptide, to a pharmaceutical composition comprising such a polypeptide, and to a kit of parts comprising at least two polypeptides of the disclosure.

1 .- 27 . (canceled) 
     
     
         28 . A single polypeptide chain comprising:
 at least four specific binding domains, the specific binding domains separated by linker amino acid sequences, wherein each specific binding domains comprises an immunoglobulin fragment.   
     
     
         29 . The single polypeptide chain of  claim 28 , further comprising:
 a peptide that is not a linker and does not comprise an immunoglobulin fragment.   
     
     
         30 . The single polypeptide chain of  claim 28 , having six specific binding domains. 
     
     
         31 . The single polypeptide chain of  claim 28 , wherein the at least one specific binding domain is a V H . 
     
     
         32 . The single polypeptide chain of  claim 28 , wherein the specific binding domains are able to bind to an MHC-I-peptide complex. 
     
     
         33 . The single polypeptide chain of  claim 32 , wherein the MHC-I-peptide complex comprises a peptide derived from a tumor related antigen. 
     
     
         34 . The single polypeptide chain of  claim 31 , wherein at least one of the specific binding domains comprises SEQ ID NO:11 or SEQ ID NO:12. 
     
     
         35 . The single polypeptide chain of  claim 31 , wherein at least one of the linker amino acid sequences comprises SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:24. 
     
     
         36 . The single polypeptide chain of  claim 31 , wherein the specific binding domains are able to bind to the MHC-peptide complex, but not to the peptide itself, another MHC-peptide complex, or an empty MHC. 
     
     
         37 . A method for producing the single polypeptide chain of  claim 28 , the method comprising:
 culturing a host cell comprising a polynucleotide encoding the polypeptide,   allowing for expression of the polynucleotide, and   harvesting the polypeptide.   
     
     
         38 . A pharmaceutical composition comprising:
 the single polypeptide chain of  claim 28 , and   a suitable diluent and/or excipient.   
     
     
         39 . The pharmaceutical composition according to  claim 38 , further comprising a cytostatic and/or tumoricidal agent. 
     
     
         40 . A conjugate of the single polypeptide chain of  claim 28 , and a cytostatic or tumoricidal agent. 
     
     
         41 . A single polypeptide chain consisting of:
 six specific binding domains, the specific binding domains separated by linker amino acid sequences, wherein each specific binding domains comprises an immunoglobulin fragment; and   a peptide that is not a linker and does not comprise an immunoglobulin fragment.   
     
     
         42 . The single polypeptide chain of  claim 41 , wherein the specific binding domains are each V H . 
     
     
         43 . A single polypeptide chain consisting of:
 six specific binding domains, the specific binding domains separated by linker amino acid sequences, wherein each specific binding domains comprises a V H ; and   a peptide that is not a linker and does not comprise a V H .