Immunotoxins: magic bullets or misguided missiles?

Thirteen years have passed since specific in vitro and in vivo killing of tumor cells by immunotoxins was first described. Why, then, has it taken so long to determine whether these pharmaceuticals will have a major impact on the treatment of cancer, AIDS and autoimmune disease? The answer is that the transfer of basic discoveries to the clinic is a slow, multistep, interdisciplinary process. Thus, immunotoxin molecules must be designed and redesigned by the basic scientist depending on the efficacy and toxicity shown in vitro and in relevant experimental models. Next, each version must be evaluated by clinicians in humans through a lengthy process (1-3 years) in which the dose regimen is optimized and in which new problems and issues frequently emerge. These problems must again be modeled and studied in animals before additional clinical trials are initiated. In this article, Ellen Vitetta and colleagues discuss both basic and clinical aspects of the development of immunotoxin therapy.