Typical Antibody–Drug Conjugates

The goal of combination chemotherapy was to increase antitumor efficacy of cytotoxic drug therapy, without substantially increasing overall toxicity to the patient, by using agents with nonoverlapping dose-limiting toxicities. Attaching cytotoxic effector molecules to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for the selective delivery of the cytotoxic payload to cancer cells via the specific binding of the antibody moiety to cancer-selective cell surface molecules. All three parts of an ADC, the antibody, the cytotoxic payload, and the linker chemistry that joins them together, are important in designing an ideal ADC. An ADC is a prodrug that can only be activated within tumor cells and is excluded from normal cells by virtue of conjugation to a protein. The proof of concept for this approach has been achieved with the approval of two ADCs bearing highly potent tubulin-acting agents, brentuximab vedotin for lymphoma, and ado-trastuzumab emtansine for metastatic HER2-positive breast cancer.