Chapter 1

Targeted Cancer Therapy: The Roles Played by Antibody-Drug and Antibody-Toxin Conjugates

Franco Dosio, Barbara Stella, Paola Milla, Carlo Della Pepa, Daniela Gastaldi and Silvia Arpicco

Abstract

In recent years, antibody therapeutics have been widely and successfully used in treating cancer. Antibodies that specifically bind tumor surface antigens can also be used as therapeutics, and over 35 of them are in clinical use (e.g. trastuzumab, bevacizumab and cetuximab). However, some unmodified antibodies against tumorspecific antigens lack therapeutic activity. Conjugation to cytotoxic agents can increase the antibodies’ activity and, at the same time, enable extremely cytotoxic drugs to be used. </p><p> Antibody-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 tumorassociated 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 forty antibody-drug conjugates and six immunotoxins now in clinical trials, as well as some recently approved drugs, support the maturity of this approach. </p><p> This chapter focuses on recent advances in the development of these two classes of biopharmaceuticals: conventional toxins and anticancer drugs are described, 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 January 2015) are lastly examined.

Total Pages: 3-103 (101)

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