Dear Colleagues,

Immunotoxins (ITxs) were born four decades ago (Nature. 1981 Mar 12;290(5802):145-6. doi: 10.1038/290145a0.), as whole bacterial or plant-derived toxin(s) conjugated to monoclonal antibodies, targeting specific antigens/receptors over-expressed at the surface of tumor cells. Compared to chemotherapy, targeted therapies show a much higher selectivity, thus helping to avoid some of the patients’ severe side-effects.

Antibodies’ target specificity/ internalization capability are key issues for the selective intracellular delivery of the toxin’s active domain. Bottlenecks have been identified, including among others avoiding cell surface recycling and degradation of the ITx, favoring toxin escape from the endomembrane system (endo-lysosomal for certain toxins or ER-Golgi retrograde transport route for other ones, to reach the cytosolic compartment) in order for them to exert their cytotoxic activity.

On the patient side, poor pharmacokinetics, vascular-leak syndrome, multi-drug resistance, and human anti-mouse antibody responses (HAMA) to both the antibody and toxin domains were tackled by switching to genetic engineering and combined recombinant approaches aiming to minimize these undesired side effects. In addition, several other novel combinatorial approaches are actively under investigation.

In a search for “immunotoxin” in PubMed, we obtained 7187 entries, 444 of which were published in the last couple of years, demonstrating that this is still a hot topic. Ligand toxins are broader ITx extensions which use targeting molecules other than antibody domains, and toxin gene delivery using nano-vector approaches, as well as novel co-adjuvant formulations, further broaden our toolbox.

In this Special Issue, we would like to invite authors to contribute regular research papers, reviews, and short communications in order to fully explore the ITx lessons from the past and indicate future paths towards innovative targeting systems to exploit the enormous potential of toxins. We would be delighted if women scientists and young investigators were willing to give their personal contribution to explore this “old” field with an emphasis on the future biomedical combined applications.

Dr. Maria Serena Fabbrini
Prof. Dr. Rodolfo Ippoliti
Guest Editors

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• plant- and bacterial-derived DNA toxin domains
• combinatorial therapy
• nanoparticle delivery
• chimeric recombinant immunotoxins
• phage-display antibody libraries
• apoptosis
• T-cell receptors
• EGF receptors
• suicide gene therapy
• peptide-driven toxin