Antibody-drug conjugate

Antibody-drug conjugates or ADCs are an important class of highly potent biopharmaceutical drugs designed as a targeted therapy for the treatment of people with cancer. Unlike chemotherapy, ADCs are intended to target and kill only the cancer cells and spare healthy cells. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are examples of bioconjugates and immunoconjugates.

By combining the unique targeting capabilities of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs, antibody-drug conjugates allow sensitive discrimination between healthy and diseased tissue. This means that, in contrast to traditional chemotherapeutic agents, antibody-drug conjugates target and attack the cancer cell so that healthy cells are less severely affected. For a video on the principles of ADCs see Nature Biotechnology Animation Antibody-drug conjugates.

In developing antibody-drug conjugates, an anticancer drug (e.g. a cell toxin or cytotoxin) is coupled to an antibody that specifically targets a certain tumor marker (e.g. a protein that, ideally, is only to be found in or on tumor cells). Antibodies track these proteins down in the body and attach themselves to the surface of cancer cells. The biochemical reaction between the antibody and the target protein (antigen) triggers a signal in the tumor cell, which then absorbs or internalizes the antibody together with the cytotoxin. After the ADC is internalized, the cytotoxic drug is released and kills the cancer. Due to this targeting, ideally the drug has lower side effects and gives a wider therapeutic window than other chemotherapeutic agents. These advantages have led to ADC technologies being featured in many publications, notably the New York Times, as well as numerous scientific journals.

To date, only three ADCs have received market approval. However, after a request from the U.S. Food and Drug Administration (FDA), Pfizer/Wyeth, the developer and marketer of the first ADC to receive marketing approval in 2001 for the treatment of patients with acute myelogenous leukemia (Gemtuzumab ozogamicin, trade name: Mylotarg®), withdrew the drug from the market in June 2010. As a result, only two ADC are marketed (2013), including Brentuximab vedotin (trade name: Adcetris®, marketed by Seattle Genetics and Millennium/Takeda) and Trastuzumab emtansine (trade name: Kadcyla, marketed by Genentech and Roche).

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