JAMA ONCOLOGY PATIENT PAGE Antibody Drug Conjugates for Cancer Treatment

Antibody drug conjugates (ADCs) are drugs designed to target specific cancer cells and release a toxic drug into the cancer cell. The Parts of an ADC and Their Importance Antibody drug conjugates work like a “smart bomb” directed against What Is an Antibody Drug Conjugate? An antibody drug conjugate (ADC) consists of chemotherapy drug cancer cells. These drugs are composed of 3 parts: an antibody drug molecules bound to an antibody by special proteins called linkers. that is specific for the type of cancer being targeted, a cytotoxic chemotherapy drug, and a linker protein to hold the 2 parts Antibody that can bind to a cancer cell together. The drug is administered, usually through a vein, and the antibody part of the drug targets the specific cancer cell protein Linker that it was made to find. When the antibody finds the protein on the proteins

outside of the cancer cell, the cell pulls the drug inside. Once inside Chemotherapy the cell, the linker releases the toxic cancer drug directly inside the molecules ADC cancer cell. By targeting the cancer cells in this way, exposure of How does an ADC work? healthy cells to the toxic cancer drug is decreased. 1 ADCs bind to receptors that NORMAL Possible Adverse Effects are found on cancer cells but CELL The adverse effects of each drug are different based on the pro- not usually on normal cells. tein it is made to target and the cytotoxic drug it contains. The CANCER cytotoxic drugs that are used to make ADCs are usually too toxic CELL to be given by themselves. The most common adverse effects are likely owing to some of the cytotoxic drug being released early into the blood before reaching the cancer cell and can include 2 The cancer cell engulfs low red and white blood cell counts, low platelet counts, nerve the ADC and the chemotherapy pain known as peripheral neuropathy, damage to the liver, and drug is released into the cell. changes in vision. 3 The drug kills the Current Roles in Cancer Treatment cancer cell without The portion of an antibody that binds to the target is highly vari- harming normal cells. able and can be individualized for specific proteins, making it pos- sible to adapt ADCs to treat a wide range of cancers. Five ADCs have been approved to treat either blood cancers or breast cancer, with many more being studied in clinical trials. • Gemtuzumab ozogamicin (Mylotarg; Pfizer) targets the CD33 re- • Ado-trastuzumabemtansine(Kadcyla;Genentech)targetstheERBB2 ceptor found on certain types of myeloid cells and is approved for protein on the surface of certain breast cancer cells and is approved relapsed acute myeloid leukemia. to treat advanced breast cancer that expresses this protein. • Brentuximab vedotin (Adcetris; Seattle Genetics) targets the CD30 receptor and is approved for certain patients with classic Hodgkin FOR MORE INFORMATION lymphoma and anaplastic large-cell lymphoma. ADCReview Journal of Antibody-Drug Conjugates • Inotuzumab ozogamicin (Besponsa; Pfizer) targets the CD22 re- https://www.adcreview.com/category/the-review/antibody-drug- ceptor and is approved for relapsed B-cell precursor acute lym- conjugates/ phoblastic leukemia. To find this and other JAMA Patient Pages, go to the For Patients • Polatuzumab vedotin-piiq (Polivy; Genentech) targets the CD79b collection at receptor and is approved in combination with certain chemo- jamanetworkpatientpages.com. therapy regimens for relapsed diffuse large B-cell lymphoma.

Authors: Christine M. Walko, PharmD; Howard (Jack) West, MD The JAMA Oncology Patient Page is a public service of JAMA Oncology.The Published Online: September 26, 2019. doi:10.1001/jamaoncol.2019.3552 information and recommendations appearing on this page are appropriate in most Author Affiliations: H. Lee Moffitt Cancer Center and Research Institute, Tampa, instances, but they are not a substitute for medical diagnosis. For specific information Florida (Walko); City of Hope Comprehensive Cancer Center, Duarte, California (West). concerning your personal medical condition, JAMA Oncology suggests that you consult your physician. This page may be photocopied noncommercially by physicians Conflict of Interest Disclosures: Dr Walko serves as a consultant to Intermountain and other health care professionals to share with patients. To purchase bulk reprints, Health Care and Jackson Genetic Laboratories outside the submitted work. Dr West email [email protected]. reports personal fees from Genentech Pfizer outside the submitted work. Section Editor: Howard (Jack) West, MD.

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