23.02.2.3. Conjugated monoclonal antibodies

Conjugated monoclonal antibodies are those antibodies that are joined to drugs, toxins or radionuclides. The antibodies are used as delivery vehicles taking those cytotoxins directly to the target cells. Although fewer in number at present than their naked counterparts, it is expected that the number of conjugated antibodies will increase in the coming years. Conjugates include ozogamycin which is a calicheamicin antibiotic, mafenatox which is an enterotoxin isolated from staphylococcus aureus and mertansine, which is a macrolide found in the staff vine plant. All of these conjugates have been demonstrated to be excellent cytotoxins, particularly useful in the killing of cancer cells.

Of the two immunotoxin thus far to receive FDA approval for treating cancer, gentuzumab ozogamycin (Mylotarg) which contains calicheamicin was used to treat acute myelogenous leukaemia (AML). It was withdrawn from market in 2010 when clinical trials demonstrated that the drug increased patient death and added no benefit over conventional cancer therapies.

The second immunotoxin, brentuximab vedotin, indicated for treat treatment of anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma was approved by the FDA in 2011. Other immunotoxins are in various stages of clinical trials including trastuzumab emtansine which shows promise for the treatment of HER2 positive breast cancers and it is expected that other immunotoxins will be approved in the coming years.

Radioimmunotherapy uses monoclonal antibodies tagged with a radionuclide to deliver cytotoxic radiation to the target cell. In 2003, the FDA approved ibritumomab tiuexetan (Zevalin) which is tagged with Yttrium-90 (⁹⁰Y) for use as a treatment for non-Hodgkin lymphoma. The following year, it approved Iodine (¹³¹I) tositumomab (Bexxar) as treatment for the same disease.