Polypeptide that binds aberrant cells and induces apoptosis
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. A single-chain polypeptide comprising at least one camelized Vh domain of an antibody functionally connected with apoptin or a fragment and/or derivative thereof, able to induce apoptosis in aberrant cells, but not normal cells,
wherein the at least one camelized Vh domain of an antibody specifically binds an MHC1-MAGE peptide.
2. The single-chain polypeptide of claim 1 , wherein the single-chain polypeptide comprises SEQ ID NO:2.
3. A single polypeptide chain comprising:
at least one domain comprising SEQ ID NO:2, wherein the domain specifically binds to an MHC1-MAGE peptide complex and wherein the at least one domain comprising SEQ ID NO:2 is linked via peptide bond with apoptin or a fragment and/or derivative thereof that upon administration to a cell induces apoptosis in an aberrant cell, but not in a normal cell.
4. A single-chain polypeptide comprising four camelized Vh domains of an antibody functionally connected with apoptin or a fragment and/or derivative thereof, able to induce apoptosis in aberrant cells, but not normal cells, wherein each of the four camelized Vh domains of an antibody specifically binds an MHC-1-MAGE peptide complex.
5. The single-chain polypeptide of claim 4 , wherein the four camelized Vh domains of an antibody are selected from the group consisting of a domain comprising SEQ ID NO:2 and a domain comprising SEQ ID NO:13.
6. The single-chain polypeptide of claim 4 , wherein the four camelized Vh domains of an antibody each comprise SEQ ID NO:2.