Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins
Franco Dosio, Barbara Stella, Sofia Cerioni, Daniela Gastaldi and Silvia ArpiccoAffiliation:
Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, v. P. Giuria 9, I-10125 Torino, Italy.
AbstractAntibody-delivered drugs and toxins are poised to become important classes of cancer therapeutics. These biopharmaceuticals have potential in this field, as they can selectively direct highly potent cytotoxic agents to cancer cells that present tumor-associated surface markers, thereby minimizing systemic toxicity. The activity of some conjugates is of particular interest receiving increasing attention, thanks to very promising clinical trial results in hematologic cancers. Over twenty antibody-drug conjugates and eight immunotoxins in clinical trials as well as some recently approved drugs, support the maturity of this approach. This review focuses on recent advances in the development of these two classes of biopharmaceuticals: conventional toxins and anticancer drugs, together with their mechanisms of action. The processes of conjugation and purification, as reported in the literature and in several patents, are discussed and the most relevant results in clinical trials are listed. Innovative technologies and preliminary results on novel drugs and toxins, as reported in the literature and in recently-published patents (up to February 2013) are lastly examined.
Antibody drug conjugate, anticancer agents, auristatins immunotoxin, calicheamicins, cross-linkers, duocarmycins, maytansinoids.
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