Engineered Bacteria as Trojan Horses in Cancer Therapy

It is indeed revolutionary how something as simple as a bacterium can be engineered to tackle such illness.

In an innovative leap for cancer treatment, researchers have engineered bacteria to act as “Trojan horses” carrying cancer-killing viruses directly into tumours. This strategy overcomes a long-time barrier in oncolytic virotherapy by delivering viruses past the body’s defences deep into solid tumours. The new work, published in Nature Biomedical Engineering, describes a system called CAPPSID (Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery). The tumour-seeking bacteria can carry a viral genome into the tumour microenvironment, circumventing immune inactivation and launching the virus inside the cancer cells.

The bacterial vector used is Salmonella typhimurium which naturally moves toward low-oxygen and nutrient-rich tumour interiors. The virus employed is Senecavirus apicornavirus, which is chosen because of its known oncolytic potential. The engineered Salmonella carries and transcribes the viral RNA inside cells. When inside the tumour, the bacteria lysis releases the viral genome into cancer cells, where it can replicate and spread. The virus has been engineered to depend on a bacterial protease for maturation. It can only form infectious viral particles in locations where the engineered bacteria are present. This acts as a safety lock, preventing the virus from replicating in healthy tissues. In mouse tumour models, the CAPSID approach cleared tumours and bypassed circulating antiviral antibodies. The built-in dependency of the virus on bacterial proteases adds a crucial safety layer, reducing the risk of the virus spreading into healthy tissues.

While promising, this approach is still in early stages. Researchers will need to verify safety and efficacy across multiple tumour types and in larger animal models before human trials. Moreover, delivering living microbes into patients raises regulatory, immunogenicity and manufacturing challenges. although it is indeed revolutionary how something as simple as a bacterium can be engineered to tackle such illness.

References:

Ben-Jacob, Eshel. "Engineering Trojan-horse bacteria to fight cancer." Blood, The Journal of the American Society of Hematology 122.5 (2013): 619-620