From Immunotoxins to Suicide Toxin Delivery Approaches: Is There a Clinical Opportunity?

Abstract

Suicide gene therapy is a relatively novel form of cancer therapy in which a gene coding for enzymes or protein toxins is delivered through targeting systems such as vesicles, nanoparticles, peptide or lipidic co-adjuvants. The use of toxin genes is particularly interesting since their catalytic activity can induce cell death, damaging in most cases the translation machinery (ribosomes or protein factors involved in protein synthesis) of quiescent or proliferating cells. Thus, toxin gene delivery appears to be a promising tool in fighting cancer. In this review we will give an overview, describing some of the bacterial and plant enzymes studied so far for their delivery and controlled expression in tumor models.

Recent Advances on Affibody- and DARPin-Conjugated Nanomaterials in Cancer Therapy

“…Furthermore, the strategy leads to the prevention of secondary tumor nodes. This example also recalls an important aspect concerning therapeutics against cancer: toxins, indeed, are currently being investigated as effective tools for their high potency and ease of production though clinical use is still missing [56].…”

“…Furthermore, the strategy leads to the prevention of secondary tumor nodes. This example also recalls an important aspect concerning therapeutics against cancer: toxins, indeed, are currently being investigated as effective tools for their high potency and ease of production though clinical use is still missing [56]. Another strategy paving the way for modern chemotherapy is based on dual targeting that makes possible improvements in both efficiency and specificity while minimizing side effects.…”

“…Biological toxic agents, such as protein domains or gene sequences, have been explored during the last decades to deliver agents into cancer cells. However, they still are subjected to two main strategies based on Ab-mediated toxin delivery or immunotoxins or the use of genes coding for toxic proteins or nonhuman enzymes, for instance, those from bacteria or plants [56,68]. Taking advantage of DARPin scaffolds, new strategies have been developed as reported, for instance, by Shipunova et al who proposed a targeted delivery of the bacterial toxin ribonuclease barnase from Bacillus amyloliquefaciens into HER2-positive human cancer cells using liposomes [69].…”

The Biological Properties of Bacterial Toxins

“…24 Для понимания технологий суицидной генной терапии можно ознакомиться с работой M. Ardini с соавт. [87]. 25 DRUGS A-Z LIST.…”

Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

“…Because of such limitations, DNA was preferred over mRNA for gene therapy development until recent years [8][9][10][11][12][13]. Specifically, viral vectors and naked or plasmid DNA were mostly investigated for suicide gene therapy purposes, using intracellular expression of a toxic protein or an enzyme that converts a non-toxic compound to a cytotoxic molecule to induce cancer cell death [8,[14][15][16][17][18][19].…”