ABSTRACT
Activation may be an issue when testing cytokine fusion toxins in which the cytokine still may have the capability of triggering activation prior to delivery of a toxic signal. Several factors might contribute to conjugate toxicity in vivo. In the majority of clinical trials, the vascular leak syndrome has occurred. In the case of cytokine fusion toxins, it could be feasible for the cytokine to trigger its receptor without enough conjugate being present to trigger toxicity. Historically, animal models have played an important role in the clinical development of immunoconjugates. Activation of cells triggered by the binding of mAb or cytokine, especially to cells of the immune system, can have toxic consequences. Fusion toxins are constructed by fusing cytokine genes or antibody genes to toxin genes. Molecular biology has given new life to the immunoconjugate field. On the one hand, toxin conjugates have major limitations in achieving doses necessary for saturation of clinical target sites, curing a given disease.
