Scientists at Columbia University have engineered a cancer treatment that leverages bacteria to smuggle cancer-killing viruses into tumors in a method that sidesteps the defenses of the immune system. This groundbreaking approach utilizes two vital weapons against the cancer; the bacteria are drawn to cancer cells, and the viruses inside the bacteria deliver the killer blow to the tumor cells after being delivered there by the bacteria.
The study team was successful in creating built-in safeguards intended to prevent the viruses from infiltrating and infecting tissues outside the tumor environment. Their research promises to introduce a new paradigm in the way targeted therapy can be offered to cancer patients.
The study findings were published in the journal Nature Biomedical Engineering. The system created takes advantage of two key features of the microbes selected. First, the bacteria (salmonella typhimurium) naturally seek out the tumor microenvironment due to the tumor having an abundance of nutrients and low levels of oxygen. These conditions are ideal for this particular bacteria species. Once inside the tumor, the bacteria release their viral payload which then gets to work killing the cancer cells.
One major concern about using viruses to attack cancer cells is that those viruses can spread and trigger a systemic infection that could be devastating for the patient. The research team addressed this major concern by engineering the oncolytic virus in such a way that as the RNA replicates inside the tumor, it requires a particular molecule to grow and spread.
That protease was only made available in the bacteria delivering the viral particles. This meant that the virus could only multiply inside the tumor and once some viruses ever got out of the tumor environment, they would be unable to access the vital protease they need to grow and multiply. Those unlikely strays can then easily be picked off by the immune system. Note that the bacteria are naturally attracted to live within the tumor microenvironment, so this safeguard limits the viral presence to the tumor cells.
For long, it has been challenging to deliver oncolytic viruses into the tumor itself because the immune system is highly sensitive to viruses and can eliminate them before they reach the tumor. The sensitivity of the immune system comes from prior infections that create antibodies against those viruses, or vaccination that primes the immune system to recognize and attack viruses.
The Trojan horse (bacteria) in this study was therefore pivotal in ensuring that the viral RNA could be hidden and delivered where it was wanted, inside the tumor. The success registered in using this approach in mouse models is now being fine-tuned to be effective against different cancers. Plans are also underway to test this therapy approach in clinical trials.
The use of oncolytic viruses in the treatment of cancer is an exciting field of research that is gaining attention, and other entities like Calidi Biotherapeutics Inc. (NYSE American: CLDI) are also registering progress in their R&D programs targeting solid tumors. It is just a matter of time before these treatments leveraging oncolytic viruses become available to patients.
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