Cysteine linked nanobody dimers

A method of killing a cancer cell having a Receptor Tyrosine Kinase on its surface, the method comprising contacting the cancer cell with a polypeptide-drug conjugate, wherein the polypeptide-drug conjugate comprises:

• (i) a dimer comprising:
• a first polypeptide comprising at least one immunoglobulin single variable domain (ISVD) and a C-terminal extension consisting of 2 to 10 amino acids and comprising a cysteine moiety, wherein the most C-terminal amino acid of the first polypeptide is not cysteine;
• and a second polypeptide comprising at least one immunoglobulin single variable domain (ISVD) and a C-terminal extension consisting of 2 to 10 amino acids and comprising a cysteine moiety, wherein the most C-terminal amino acid of the second polypeptide is not cysteine;
• and
• (ii) a cytotoxic drug conjugated to the dimer;
• wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety in the C-terminal extension of said first polypeptide and the cysteine moiety in the C-terminal extension of said second polypeptide;
• and said disulfide bond between the cysteine moiety in the C-terminal extension of said first polypeptide and the cysteine moiety in the C-terminal extension of said second polypeptide is the only intermolecular disulfide bond present in the dimer, and
• wherein at least said first polypeptide binds to the Receptor Tyrosine Kinase on the surface of the cancer cell, and upon binding is capable of being internalized by the cancer cell.