Single-Chain Fusion Toxins for the Treatment of Breast Cancer: Antitumor Activity of BR96 sFv-PE40 and Heregulin-PE40

Abstract

Many commonly used anti-cancer drugs have been identified through massive screenings of natural products and chemical compounds. Unfortunately, these screens have resulted in the selection of compounds that are not only cytotoxic to cancer cells, but to most actively proliferating cells as well. The small degree of selectivity usually lies in the fact that cancer cells are amongst the most rapidly proliferating of all cell types in the body. A different approach to the development of anti-cancer therapeutics is through rational design of targeted cytotoxic agents. These molecules are delivered to specific cell-surface receptors or antigens, usually by monoclonal antibodies (MAbs) or growth factor/cytokines, and have been appended to a variety of cytotoxic agents. These molecules include drug-immunoconjugates (Trail et al. 1993), enzyme-prodrugs (Senter et al. 1988), radiolabeled-antibodies (Press et al. 1993), and immunotoxins (Chaudhary et al. 1989) and have been used in vitro, in vivo, and clinically to target cancer cells for elimination. This article will focus on two recently developed immunotoxins, BR96 sFv-PE40 and HAR-TX ß2, and will describe their component structure, expression, purification, and preclinical characterization.