Clostridium Bacteria: Harnessing Tumour Necrosis for Targeted Gene Delivery

AbstractNecrosis is a common feature of solid tumours that offers a unique opportunity for targeted cancer therapy as it is absent from normal healthy tissues. Tumour necrosis provides an ideal environment for germination of the anaerobic bacteriumClostridium from endospores, resulting in tumour-specific colonisation. Two main species,Clostridium novyi-NT andClostridium sporogenes, are at the forefront of this therapy, showing promise in preclinical models. However, anti-tumour activity is modest when used as a single agent, encouraging development ofClostridium as a tumour-selective gene delivery system. Various methods, such as allele-coupled exchange and CRISPR –cas9 technology, can facilitate the genetic modification ofClostridium, allowing chromosomal integration of transgenes to ensure long-term stability of expression. Strains ofClostridium can be engineered to express prodrug-activating enzymes, resulting in the generation of active drug selectively in the tumour microenvironment (a concept termedClostridium-directed enzyme prodrug therapy). More recently,Clostridium strains have been investigated in the context of cancer immunotherapy, either in combination with immune checkpoint inhibitors or with engineered strains expressing immunomodulatory molecules such as IL-2 and TNF- α. Localised expression of these molecules using tumour-targetingClostridium strains has the potential to improve delivery and reduce systemic toxicity. In summary,Clostridium species represe...

Source: Molecular Diagnosis and Therapy - February 2, 2024 Category: Molecular Biology Source Type: research