《Antibody-Drug Conjugates for the Treatment of Cancer》.pdf

Chem Biol Drug Des 2013; 81: 113–121 Special Issue-Review Cancer Treatment and Personalized Medicine Antibody-Drug Conjugates for the Treatment of Cancer 1 1 powerful cytotoxic agent to a tumor cell has the potential John A. Flygare *, Thomas H. Pillow and Paul Aristoff2 to broaden the therapeutic index of these treatments. Evi- dence for the validity of this approach continues to 1Department of Discovery Chemistry, Genentech, Inc., 1 emerge, for example, brentuximab vedotin (SGN-35, Ad- DNA Way, South San Francisco, CA 94080, USA cetris) was approved by the FDA in August of 2011, and 2Aristoff Consulting, LLC, Dexter, MI 43180, USA there are currently over 20 ADCs in clinical development *Corresponding author: John Flygare, (2–4). flygare.john@ The ADC components consist of an antibody, a cytotoxic With over 20 antibody-drug conjugates in clinical trials drug, and a linker that attaches the two (Fig. 1A) (4–11). as well as a recently FDA-approved drug, it is clear The monoclonal antibody binds to an antigen that is selec- that this is becoming an important and viable tively expressed on the surface of a tumor cell. Upon bind- approach for selectively delivering highly cytotoxic ing, the antibody gets absorbed into the cell via receptor- agents to tumor cells while sparing normal tissue. This mediated endocytosis and the antibod