Since its reemergence following the discovery of monoclonal antibodies in the early 1980s, the field of antibody therapy in cancer has progressed in leaps and bounds. From murine to chimeric, through humanized to fully human, we are now in a situation where, with over 200 antibodies having passed through some kind of clinical testing (Reichert & Valge-Archer, 2007), the monoclonal is now an accepted form of treatment for malignancy. In fact, for some malignancies, most notably non-Hodgkin's lymphoma, monoclonals are routinely used as frontline therapy. As such, we are past the point of asking whether monoclonal therapy works and into the more expansive territory of asking how it works and how we can make it work better.

While antibodies can function to combat a tumor in a number of ways – for example, sequestration of factors essential to survival or growth and stimulation of the immune response – one of the best-studied mechanisms of action is direct tumor cell killing. Here we will begin by looking in detail at the mechanisms by which antibodies can mediate cell killing, and which of these mechanisms is likely to be most important. Subsequently, we will review briefly the possible ways that this cell killing can be increased through the process of protein engineering, several of which will be expanded upon by the authors of subsequent chapters.