Is margituximab classified as an ADC drug?

Margetuximab (margetuximab-cmkb) is a monoclonal antibody drug targeting HER2, but strictly speaking, it does not belong to the category of antibody-drug conjugate (ADC). ADC drugs refer to complexes formed by combining monoclonal antibodies and cytotoxic drugs through chemical linkers. They can accurately deliver cytotoxins to tumor cells, thereby increasing the drug's lethality while reducing damage to normal cells. The mechanism of action of margetuximab is closer to that of traditional monoclonal antibodies. It binds to the HER2 receptor to block its signaling and activates effector mechanisms in the immune system, such as antibody-dependent cell-mediated cytotoxicity (ADCC), to exert anti-tumor effects.

Specifically, margetuximab is based on trastuzumab (trastuzumab). Through the engineering of the Fc segment, it enhances its affinity for the Fcγ receptor CD16A in immune cells, thereby significantly improving ADCC activity. This modification allows magituximab to show better clinical effects in the treatment of patients with HER2-positive breast cancer, especially those who are resistant to trastuzumab. It achieves a more effective anti-cancer effect by improving the ability of immune effector cells to recognize and kill tumor cells. This is fundamentally different from the mechanism in which ADC drugs directly carry cytotoxins into cancer cells.

In addition,ADC drugs usually contain stable linkers connecting monoclonal antibodies and small molecule drugs in their chemical structures, which can kill cancer cells after releasing cytotoxins. For example,EmtansineTrastuzumab emtansine (T-DM1) is a classic HER2-targeted ADC drug. In contrast, margetuximab does not contain a cytotoxic component and does not have a chemical linker to conjugate small molecule drugs, so it cannot be classified as an ADC. It is still a "naked antibody" that achieves therapeutic effects through immune system activation and signal blocking.

Reference materials:https://www.margenza.com/