Drug-conjugated bi-specific antigen-binding constructs

A method of killing target cells that express a target antigen on the cell surface comprising:

• contacting the target cells with an effective amount of a drug-conjugated antigen-binding construct in the presence of effector T cells, wherein the drug-conjugated antigen-binding construct comprises an antigen binding construct conjugated to mertansine (DM1) with a N-succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (SMCC) linker and the antigen-binding polypeptide construct comprises a first antigen-binding polypeptide construct operably linked to a second antigen-binding polypeptide construct, wherein
• the first antigen-binding polypeptide construct specifically binds a CD3 epsilon antigen expressed on the effector T cells and is an scFv and comprises a first heavy chain variable (VH) region comprising SEQ ID NO:213 and a first light chain variable (VL) region comprising SEQ ID NO:221;
• and
• the second antigen-binding polypeptide construct comprising a second VH region comprising a CDR1, a CDR2, and a CDR3 and a second VL region comprising a CDR1, a CDR2, and a CDR3, wherein the second antigen binding polypeptide is an scFv or a Fab and specifically binds the target antigen and
• the target antigen is CD19, and the second VH CDR1 comprises SEQ ID NO:591, the second VH CDR2 comprises SEQ ID NO:595, the second VH CDR3 comprises SEQ ID NO:593, the second VL CDR1 comprises SEQ ID NO:607, the second VL CDR2 comprises SEQ ID NO:611, and the second VL CDR3 comprises SEQ ID NO:609;
• or
• the target antigen is CDH3, and the second VH CDR1 comprises SEQ ID NO:139, the second VH CDR2 comprises SEQ ID NO:143, the second VH CDR3 comprises SEQ ID NO:141, the second VL CDR1 comprises SEQ ID NO:683, the second VL CDR2 comprises SEQ ID NO:687, and the second VL CDR3 comprises SEQ ID NO:685;
• or
• the target antigen is HER2, and the second VH CDR1 comprises SEQ ID NO:199, the second VH CDR2 comprises SEQ ID NO:203, the second VH CDR3 comprises SEQ ID NO:201, the second VL CDR1 comprises SEQ ID NO:823, the second VL CDR2 comprises SEQ ID NO:827, and the second VL CDR3 comprises SEQ ID NO:825;
• or
• the target antigen is HER3 and the second VH CDR1 comprises SEQ ID NO:667, the second VH CDR2 comprises SEQ ID NO:671, the second VH CDR3 comprises SEQ ID NO:669, the second VL CDR1 comprises SEQ ID NO:795 the second VL CDR2 comprises SEQ ID NO:799, and the second VL CDR3 comprises SEQ ID NO:797;
• or
• the target antigen is EGFR, and the second VH CDR1 comprises SEQ ID NO:651, the second VH CDR2 comprises SEQ ID NO:653, the second VH CDR3 comprises SEQ ID NO:655, the second VL CDR1 comprises SEQ ID NO:403, the second VL CDR2 comprises SEQ ID NO:407, and the second VL CDR3 comprises SEQ ID NO:405.