| abstract |
Cytotoxic protein comprising: a) an immunoglobulin-like binding region comprising one or more polypeptides and capable of specifically binding to at least one extracellular target biomolecule, wherein said immunoglobulin-like binding region is derived from an antibody, wherein said extracellular target biomolecule is HER2 / neu / ErbB2; and b) a Shiga toxin effector region comprising a polypeptide that is capable of effecting the cytotoxicity of Shiga toxin Subunit A, and comprises: an amino acid sequence that is at least 90% identical to the amino acid sequence shown. in any of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3; or an amino acid sequence selected from: (i) amino acids 75 to 251 of SEQ ID No: 1, SEQ ID No: 2 or SEQ ID No: 3; (ii) amino acids 1 to 241 of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3; (iii) amino acids 1 to 251 of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3; and (iv) amino acids 1 to 261 of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3, in which the protein is capable of causing the death of a cell physically coupled with said HER2 / neu / ErbB2 ; and wherein the Shiga toxin binding region and effector region are oriented within the protein such that the binding region is in a position that is closer to the carboxy terminal end of the Shiga toxin effector region than to the amino terminus of the effector region of Shiga toxin. |