Using bacteria as a “Trojan Horse”, scientists at Columbia University and Rockefeller University deliver viruses directly into tumours, bypassing the body’s immune system. Bacteria and viruses then work together to mount a powerful attack on cancer cells. The findings are published in the latest issue of the journal Nature Biomedical Engineering.
This“Trojan Horse” system cleverly combines the ability of bacteria to find and attack tumors with the innate ability of viruses to infect and kill cancer cells. Multiple security mechanisms are built into the system to ensure that the virus will not reproduce outside the tumor, providing a new way to achieve safe and accurate targeted cancer therapy.
The team says the technique, which has been shown to work in mice, is the first example of direct engineering of bacteria to work with cancer-fighting viruses, setting the stage for the development of multi-biological combination therapies. Such therapies hold promise for therapeutic effects that can not be achieved by a single microbe.
Oncolytic virotherapy is a therapeutic strategy that uses natural or genetically modified viruses to specifically infect and destroy cancer cells, especially in the field of brain tumors. However, one of the major challenges facing the therapy is the body’s own immune defense mechanisms. If the patient has developed antibodies to the virus because of previous infections or vaccination, these antibodies may clear the virus before it reaches the tumor.
The team successfully circumvented this barrier by“Hiding” the virus in bacteria that are good at tracking tumors. Experiments have shown that bacteria (some of which are Salmonella enterica) can be used to deliver oncolytic viruses to treat solid tumors that have developed immunity to the virus.
The latest progress marks an important step forward in the future clinical application of this bacteria-virus combination system. The team is testing the feasibility of this approach in more types of tumors, mouse models, viruses and payloads, and is working to develop a toolkit of viral therapies that can sense and respond to specific conditions within cells. They are also exploring the possibility of combining the system with strains of bacteria that have proved safe in clinical trials.