The ability to program living cells to behave in specific ways under certain conditions creates new opportunities in medicine. A recent mouse study in which researchers have programmed bacteria to fight against cancer is one example.

scientist working with a petri dish and a DNA code on a screen
The scientists were able to reprogram the bacteria and use them in the fight against cancer.
Some tumors develop and spread because their cells send a "do not eat me" signal that forces the immune system to leave them alone. Tumor cells that do not signal are vulnerable to macrophages and other immune cells that can engulf and digest them.

Scientists at Columbia University in New York have shown that it is possible to program bacteria to disable the signal from eating and induce an anti-tumor immune response.

This approach is an example of synthetic biology, an emerging field in which medical treatments promise to be more effective and specific than many molecular methods.

In a recent article in Nature Medicine, researchers describe how they programmed bacteria and used them to reduce tumors and increase survival in a mouse model of lymphoma.

They found that the treatment not only reduced the tumors they had injected, but that distant , secondary tumors or metastases also responded.

"Seeing untreated tumors respond in parallel to treatment of primary lesions was an unexpected discovery," says lead co-author Tal Danino, an assistant professor of biomedical engineering at Columbia University.

Example of an abscopal effect

Danino states that what they witnessed was the first demonstration of an "abscopal effect" in the treatment of cancer using bacteria.

"This means," he says, "that we can design bacteria to start tumors locally and then encourage the immune system to look for tumors and metastases that are too small to be detected by imaging or other approaches. "

In anticancer therapy, the abscopal effect is the ability to elicit an anti-tumor response that destroys cancer cells away from the primary target.

Cells that send me do not eat signals are common not only in tumors but also in healthy tissue. This poses a challenge to the developers of immunotherapies that target the signal.

Danino and his colleagues took up the challenge by programming bacteria to release their signal neutralization payload only when they could sense that they were in the "tumor microenvironment".

E. coli with coded nanobodies

The payload itself was in the form of a "coded nanobodies" and the bacterium used was a "non-pathogenic Escherichia coli strain".

In tumors, E. coli bacteria proliferate in necrotic nuclei, or pockets of dying cells.

The team programmed the bacteria to detect quorum, which means that when they reached a certain population size, they died and released their payload of coded nanobodies.

This strategy prevented bacteria from entering other tissues and silencing the "do not eat me" signals in their cells. However, it also left enough bacterial cells to form a new population, which resulted in repeated cycles of drug delivery into the tumor.

The team had already demonstrated such a drug distribution strategy in previous work.

In the new study, they have shown that it can also selectively disable not devouring signals in cancer cells by targeting CD47, the protein that sends the signal.

Priming T cells infiltrating the tumor

The team suggests that the treatment works because it does two things. First, the presence of live bacteria induces local inflammation in the tumor. This calls the immune system.

The second thing the treatment does is to induce immune cells, such as macrophages, to ingest the tumor cells because they deactivate their CD47 do not eat me the signal. In turn, this immune response primes the "tumor invading T cells" that then migrate to distant metastases.

The researchers suggest that the results are "a proof of concept for an abscess effect induced by artificial bacterial immunotherapy" and conclude:

"Thus, the modified bacteria can be used for safe and secure local delivery of immunotherapeutic payloads leading to systemic anti-tumor immunity. "

They are already testing the safety and effectiveness of the method with other types of cancer in mice. After that, they hope to conduct clinical trials in humans