Engineered Bacteria Show Promise in Delivering Cancer Drugs to Tumors in Mice

Engineered bacteria are showing promise as a targeted delivery system for cancer drugs, with a recent study demonstrating successful tumor colonization and drug release in a mouse model. The research, published March 17th in PLOS Biology, details how scientists at Shandong University in China engineered Escherichia coli Nissle 1917 (EcN) to synthesize and deliver the anti-cancer drug Romidepsin (FK228) directly into cancerous tumors.

A Novel Approach to Cancer Treatment

Millions are diagnosed with cancer each year, and current treatments often struggle with the complexity of the disease. This study explores a new avenue: leveraging the natural ability of bacteria to interact with the human body, specifically by modifying a probiotic strain to target and treat tumors. Even as engineered bacteria-based cancer therapies are still in early stages, this research offers a potentially significant step forward.

The team chose Escherichia coli Nissle 1917 (EcN) due to its probiotic properties and potential for tumor colonization. Using genetic and genomic engineering techniques, they created a strain capable of producing Romidepsin, an FDA-approved drug already used in cancer treatment. The researchers then introduced this engineered bacteria into mice with breast cancer tumors.

The results were encouraging. The EcN bacteria successfully colonized the tumors and released Romidepsin both in vitro (in a lab setting) and in vivo (within a living organism), effectively acting as a tumor-targeted therapy. This targeted approach could potentially minimize the side effects often associated with traditional chemotherapy, which affects both cancerous and healthy cells.

Understanding the Science: Romidepsin and Tumor Colonization

Romidepsin, too known as FK228, is a histone deacetylase (HDAC) inhibitor. According to the National Cancer Institute, HDAC inhibitors work by interfering with the enzymes that remove acetyl groups from histones, proteins around which DNA is wrapped. This interference can lead to changes in gene expression, ultimately promoting cancer cell death.

The key innovation in this study isn’t just the use of Romidepsin, but how it’s delivered. Traditional drug delivery often relies on systemic administration, meaning the drug travels throughout the body. This can lead to off-target effects and require higher doses to achieve therapeutic concentrations at the tumor site. By engineering bacteria to colonize tumors and produce the drug locally, researchers aim to maximize efficacy while minimizing systemic toxicity.

Study Details and Limitations

The study, led by Tianyu Jiang at Shandong University, involved creating a mouse model with tumor-producing breast cancer cells. The researchers meticulously engineered the EcN strain to synthesize Romidepsin and then monitored its colonization of tumors and subsequent drug release. The findings, detailed in the publication “Engineered romidepsin biosynthetic pathways in Escherichia coli Nissle 1917 improve the efficacy of bacteria-mediated cancer therapy” in PLOS Biology, demonstrate the feasibility of this approach.

However, it’s crucial to acknowledge the limitations. This research was conducted in a mouse model, and results may not directly translate to humans. Further studies are needed to assess the safety and efficacy of this treatment in human subjects. The authors themselves highlight the need for research into potential adverse outcomes and methods for eliminating the bacteria after treatment, as persistent bacteria could pose unforeseen risks.

What Comes Next: From Mouse Models to Human Trials

The next steps involve rigorous pre-clinical testing to further evaluate the safety and efficacy of engineered EcN. This includes optimizing the bacterial strain, refining drug delivery mechanisms, and conducting more comprehensive toxicity studies. If these pre-clinical studies are successful, the researchers will likely seek approval to initiate Phase 1 clinical trials in humans. These trials will primarily focus on assessing the safety of the treatment and determining the appropriate dosage.

A significant challenge will be developing strategies to control the bacteria once the drug has been delivered. Researchers need to ensure the bacteria can be effectively eliminated after treatment to prevent any long-term complications. This could involve using antibiotic therapies or engineering the bacteria with self-destruct mechanisms.

The Broader Context of Bacterial Cancer Therapies

This study builds upon a growing body of research exploring the potential of engineered bacteria in cancer therapy. Other research has investigated using bacteria to deliver different types of anti-cancer agents, stimulate the immune system to attack tumors, or even directly kill cancer cells. The field is still relatively young, but the initial results are promising.

The use of probiotic strains like EcN is particularly attractive because of their inherent safety profile and ability to interact with the gut microbiome, which plays a crucial role in immune function and overall health. However, it’s important to remember that even probiotic strains can pose risks in certain individuals, particularly those with compromised immune systems.

As Tianyu Jiang and colleagues note, “Our mouse-model study establishes a solid foundation for engineering bacteria which are capable of producing small-molecule anticancer drugs and engaged in bacteria-assisted tumor-targeted therapy, paving the way for future advancements in this field.” While significant hurdles remain, this research offers a glimmer of hope for more effective and targeted cancer treatments in the future.