Mechanism of cysteine-mcMMAF release from the stably linked antibody-drug conjugate SGN-75
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X Zhang, NM Okeley, J Setter, CL Law…
Cancer …, 2010
aacrjournals.org
The antibody-drug conjugate SGN-75 is composed of the humanized monoclonal antibody (mAb) h1F6 and the drug-linker mcMMAF conjugated through interchain disulfide cysteine residues. SGN-75 has been shown to be highly active against tumor cell lines both in vitro and in vivo. The mcMMAF drug-linker was designed to be protected from protease cleavage, and we have shown that cysteine-mcMMAF is the major released drug in vitro. We demonstrate that the cysteine residue in cysteine-mcMMAF comes from the mAb, implying …