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Antibody drug conjugates (ADCs) are drugs designed to target specific cancer cells and release a toxic drug into the cancer cell.
Antibody drug conjugates work like a “smart bomb” directed against cancer cells. These drugs are composed of 3 parts: an antibody drug that is specific for the type of cancer being targeted, a cytotoxic chemotherapy drug, and a linker protein to hold the 2 parts together. The drug is administered, usually through a vein, and the antibody part of the drug targets the specific cancer cell protein that it was made to find. When the antibody finds the protein on the outside of the cancer cell, the cell pulls the drug inside. Once inside the cell, the linker releases the toxic cancer drug directly inside the cancer cell. By targeting the cancer cells in this way, exposure of healthy cells to the toxic cancer drug is decreased.
The adverse effects of each drug are different based on the protein it is made to target and the cytotoxic drug it contains. The cytotoxic drugs that are used to make ADCs are usually too toxic 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 low red and white blood cell counts, low platelet counts, nerve pain known as peripheral neuropathy, damage to the liver, and changes in vision.
The portion of an antibody that binds to the target is highly variable and can be individualized for specific proteins, making it possible 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 receptor found on certain types of myeloid cells and is approved for relapsed acute myeloid leukemia.
Brentuximab vedotin (Adcetris; Seattle Genetics) targets the CD30 receptor and is approved for certain patients with classic Hodgkin lymphoma and anaplastic large-cell lymphoma.
Inotuzumab ozogamicin (Besponsa; Pfizer) targets the CD22 receptor and is approved for relapsed B-cell precursor acute lymphoblastic leukemia.
Polatuzumab vedotin-piiq (Polivy; Genentech) targets the CD79b receptor and is approved in combination with certain chemotherapy regimens for relapsed diffuse large B-cell lymphoma.
Ado-trastuzumab emtansine (Kadcyla; Genentech) targets the ERBB2 protein on the surface of certain breast cancer cells and is approved to treat advanced breast cancer that expresses this protein.
ADCReview Journal of Antibody-Drug Conjugateshttps://www.adcreview.com/category/the-review/antibody-drug-conjugates/
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Published Online: September 26, 2019. doi:10.1001/jamaoncol.2019.3552
Conflict of Interest Disclosures: Dr Walko serves as a consultant to Intermountain Health Care and Jackson Genetic Laboratories outside the submitted work. Dr West reports personal fees from Genentech Pfizer outside the submitted work.
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Walko CM, West H. Antibody Drug Conjugates for Cancer Treatment. JAMA Oncol. Published online September 26, 2019. doi:10.1001/jamaoncol.2019.3552
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