Target-switchable modular bacterial toxin delivery system

Abstract

Statement of Purpose: Recombinant immunotoxins (RITs) have been extensively utilized in the field of targeted cancer therapy. RITs are composed of toxins derived from natural bacterial strains and antibodies for target specific toxin delivery, causing fatal effects on the cancer cells. However, low intracellular penetration and endosomal escape efficiency of toxin part has limited the application of the RITs. The diphtheria toxins are produced by bacteria, Corynebacterium diphtheriae, and belong to AB toxin families which consist of catalytic (A) domain, binding (B) domain, and translocation (T) domain. Once the B domain binds to the specific target receptors, it facilitates the receptor-mediated endocytosis. At the endosome, T domain delivers A domain to cytosol, resulting in cell apoptosis (Figure 1).