Drug-conjugated monoclonal antibodies for the treatment of cancer

Abstract

Early clinical development in the field of targeted delivery of cytotoxic drugs to tumors was not successful because the limitations imposed by the pharmacokinetic and pharmacodynamic properties of monoclonal antibodies were not fully appreciated. Recently, development of this concept has been reinvigorated by the approval of gemtuzumab ozogamicin for treatment of acute myeloid leukemia. Other conjugates of calicheamicin and conjugates of potent tubulin poisons (maytansinoids auristatins and taxoids) are undergoing clinical evaluation or are in preclinical development. What all of these drugs have in common is that their cytotoxic potencies are in the picomolar range. Thirty years after the discovery of monoclonal antibodies, this new generation of highly potent compounds could yield targeted cytotoxic agents that are effective treatments for many cancers.