Innovative Bioengineering Technique Utilizes Bacteria to Deliver Viruses to Tumors

Researchers at Columbia University have developed an advanced cancer treatment that effectively combines the capabilities of bacteria and viruses. In a groundbreaking study published in Nature Biomedical Engineering, the Synthetic Biological Systems Lab demonstrated how this novel system can encapsulate a virus within a bacterium that targets tumors, allowing it to bypass the immune system and release the virus directly into cancerous cells.

This innovative platform leverages the natural ability of bacteria to locate and invade tumors, paired with the virus's effectiveness in infecting and destroying cancer cells. The project, led by a team of engineers and virologists, introduces a system named CAPPSID (Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery), which aims to enhance the efficacy of bacterial therapies by facilitating the direct delivery of therapeutic viruses.

The primary objective of this research is to unlock the potential of engineered bacteria to transport and activate a virus within tumor cells, while also incorporating mechanisms to prevent the virus from spreading to healthy tissues. This represents a significant advancement in the field, marking the first instance of engineered collaboration between bacteria and oncolytic viruses.

One of the major challenges in using oncolytic viruses for cancer treatment is the human immune response, which can neutralize the virus before it reaches the tumor site. The researchers tackled this issue by using bacteria as a protective vehicle, effectively disguising the virus from the immune system. By programming the bacteria to act as an 'invisibility cloak,' they managed to shield the virus from circulating antibodies, delivering it precisely where it is needed.

The bacterial strain utilized in this study, Salmonella typhimurium, is known for its ability to thrive in the hypoxic and nutrient-rich environment found within tumors. Once the bacteria infiltrate the tumor, they release the virus directly into the cancer cells. This strategic design allows for a Trojan horse effect, whereby the bacteria deliver the viral RNA into the tumor and subsequently lysate themselves to release the viral genome, which can then propagate among the cancer cells.

Moreover, the researchers implemented a safeguard to control the virus's spread beyond the tumor. By ensuring that the virus requires a specific bacterial enzyme to replicate, they created a scenario where viral particles can only mature in the presence of the bacteria, providing a synthetic dependency that limits potential infections in healthy tissues.

This research represents a crucial step toward translating these bacterial and viral therapies into clinical applications. The authors are currently exploring various cancer types and testing different virus strains, with the goal of developing a comprehensive toolkit of viral therapies that can adapt to specific cellular conditions.

As further studies continue, the team is also investigating the possibility of integrating bacterial strains that have previously shown safety in clinical trials, paving the way for future treatments that harness the power of engineered microorganisms to combat cancer.