Cancer: “Trojan horse” bacteria reprogrammed to destroy tumors

Living cells “Trojan horse”. This is how the authors of this new study qualify these bacteria reprogrammed to destroy tumors and which constitute new hope in the fight against cancer.

In the magazine NatureMedicine, researchers from Columbia Engineering and the Columbia University Irving Medical Center (CUIMC) have announced that they have succeeded in creating a strain of non-pathogenic bacteria that are able to eliminate tumors in laboratory mice, but also to treat tumors that were not initially targeted. Ultimately, this new method could be used to locally target cancer cells, but also stimulate the immune system to defend itself against hard-to-treat tumours.

Infiltration at the heart of tumors

In their work, the scientists explain that they have developed a strain of bacteria E.coli non-pathogenic, capable of growing and multiplying in the necrotic nucleus of tumors. Once their number reaches a critical threshold, they self-destruct, allowing a release of therapeutic agents. Only a small fraction of the bacteria survive to continue delivering treatment to the core of tumors.

To make these bacteria particularly effective, the authors of the study chose to target a protein called CD47 and present in abundance in human tumor cells. This CD47 protein sends a “don’t eat me” signal to immune cells so that they don’t eat cancer cells.

“But CD47 is present elsewhere in the body, and systemic targeting of CD47 leads to significant toxicity as evidenced by recent clinical trials,” says Sreyan Chowdhury, co-author of the study. “To solve this problem, we designed bacteria that target CD47 exclusively inside the tumor and avoid the systemic side effects of treatment.”

A reduction in non-targeted tumors

This combined effect of the action of the bacteria inside the tumors and the blocking of CD47 allowed a stimulation of the immune system, with a proliferation of T lymphocytes in the treated tumors. Not only did this have the effect of eliminating specifically targeted tumors, but also of reducing tumor metastases that were not targeted by the treatment.

“This means that we will soon be able to engineer bacteria to target tumors locally and then stimulate the immune system to seek out tumors and metastases that are too small to be detected by imaging or other approaches,” says Tal Danino, assistant professor of biomedical engineering and co-author of the study.

The scientific team is currently performing further trials to validate their discovery, as well as safety and toxicology studies on the modified immunotherapeutic bacteria. If the results are positive, this could lead to a clinical trial on human patients.