Chinese scientists reveal key mechanism behind bacterial cancer therapy

SHENZHEN -- A new study by Chinese scientists has uncovered the mechanism behind bacterial cancer therapy using a genetically engineered bacterial strain in a breakthrough that offers new hope for the development of next-generation cancer therapies.

The findings of the joint research team from the Shenzhen Institutes of Advanced Technology (SIAT) and the Shanghai Institute of Nutrition and Health, both under the Chinese Academy of Sciences, were published online by the journal Cell.

Exploring the use of antitumor bacteria in cancer therapy dates back to the 1860s. Despite this long history, clinical application of bacterial-based cancer therapy has faced significant challenges in terms of safety and efficacy.

Recent advancements in synthetic biology have enabled the development of novel antitumor bacteria, creating new avenues for immuno-oncology research. However, such bacteria's practical application has been hindered by the unclear mechanisms by which they evade host immune defenses while activating antitumor responses, according to Liu Chenli, one of the project's leading scientists from SIAT.

In this study, researchers engineered an attenuated strain of bacteria, named Designer Bacteria 1 (DB1), which efficiently survives and proliferates in tumor tissues while being cleared in normal tissues, achieving a remarkable "tumor-targeting" effect as well as "tumor-clearing" effect.

To understand how DB1 simultaneously achieves these effects, researchers investigated the interactions between the bacteria and tumors. They discovered that DB1's antitumor efficacy is closely linked to tissue-resident memory cytotoxic T cells within the tumor, which are reinvigorated and expanded following DB1 therapy. In addition, in tumors, DB1 can slow down the migration of neutrophils, which helps with the survival of bacteria in the "target."

They also found that the signaling molecule, interleukin-10, plays a crucial role in mediating these effects, with efficacy depending on the high expression of interleukin-10 receptor on the T cells and neutrophils in tumors only.

"Our findings illuminate a crucial, yet previously unresolved mechanism in bacterial cancer therapy. This mechanism not only provides valuable insights but also serves as a guiding principle for the design of engineered bacteria, enhancing safety and efficacy," Liu said.

The researchers validated this therapy in various animal models, and the results showed that this synthetically bioengineered bacteria significantly inhibits the growth, recurrence and metastasis of multiple types of tumors.

Currently, this research is being advanced toward clinical trials, and will provide a scientific basis for the formulation of personalized treatment plans in the future, according to Liu.

The engineered antitumor bacteria can also serve as delivery carriers, enabling precise release of therapeutic drugs and opening up a new pathway for the treatment of malignant tumors, he added.