Bispecific CD33 and CD3 binding proteins

A method for the treatment of acute myelogenous leukemia (AML) comprising the administration to an individual suffering from a CD33+ cancer a bispecific, antigen-binding tandem diabody specific to human CD33 and human CD3, wherein said tandem diabody comprises a first polypeptide and a second polypeptide, each polypeptide having at least four variable chain domains linked one after another, wherein each polypeptide comprises:

• (i) a variable heavy chain (VH) domain specific to human CD33;
• (ii) a variable light chain (VL) domain specific to human CD33;
• (iii) a VH domain specific for human CD3, and
• (iv) a VL domain specific for human CD3,
• and wherein in each polypeptide, the four variable chain domains are linked with one after another by peptide linkers L1, L2 and L3 in the order of:
• VL(CD3)-L1-VH(CD33)-L2-VL(CD33)-L3-VH(CD3);
• VH(CD3)-L1-VL(CD33)-L2-VH(CD33)-L3-VL(CD3);
• VL(CD33)-L1-VH(CD3)-L2-VL(CD3)-L3-VH(CD33);
• or
• VH(CD33)-L1-VL(CD3)-L2-VH(CD3)-L3-VL(CD33),
• wherein the VL domain specific to human CD33 comprises a CDR1 consisting of the sequence selected from the group consisting of SEQ ID NOs:21-27, a CDR2 consisting of the sequence selected from the group consisting of SEQ ID NOs:28-34 and a CDR3 consisting of the sequence of the group consisting of SEQ ID NOs:35-41, and
• wherein the VH domain specific to human CD33 comprises a CDR1 consisting of the sequence selected from the group consisting of SEQ ID NOs:42-48, a CDR2 consisting of the sequence selected from the group consisting of SEQ ID NOs:49-55 and a CDR3 consisting of a sequences selected from the group consisting of SEQ ID NOs:56-63.