Antibody–Cytotoxic Compound Conjugates for Oncology

The original rationale underlying the development of antibody–cytotoxic compound conjugates (ACC) was to improve the selectivity of cytotoxic anti-cancer drugs by targeting them to tumors with the help of antibodies. The ACC concept has since matured significantly, following several key advancements: (i) generation of technologies for creating humanized and fully human monoclonal antibodies; (ii) development of conjugatable cytotoxic compounds of sufficient potency to be effective in eradicating tumor cells in an antigen-selective manner; (iii) advances in knowledge and antibody engineering to maximize anti-tumor cell effect or functions; and (iv) optimization of linkers used to conjugate cytotoxic compounds to antibodies in order to achieve both maximal stability of the ACC in the circulation and maximal release of the active cytotoxic component within targeted tumor cells. In this chapter we will focus on our present understanding of what makes an effective ACC for the treatment of oncology patients. We will discuss parameters that are important for the selection of antigen targets, antibodies, cytotoxic compounds, and linkers, and current approaches being taken to further improve the efficacy of ACCs. In addition, we will review preclinical and clinical experiences with the current generation of ACCs.