Scientists at the University of Massachusetts Amherst, in collaboration with Ernest Pharmaceuticals, have developed a groundbreaking bacterial therapy named BacID. This innovative approach utilizes non-toxic, genetically engineered bacteria to deliver cancer-fighting drugs directly into tumors. BacID offers a highly targeted and safe alternative to traditional treatments, showing great promise in combating high-mortality cancers such as liver, ovarian, and metastatic breast cancer. Clinical trials involving cancer patients are expected to begin in 2027.
A Decade of Research Culminates in Breakthrough
The development of BacID is the result of over ten years of intensive research led by Neil Forbes, professor of chemical engineering at UMass Amherst, and Vishnu Raman, the study’s lead author and chief scientific officer of Ernest Pharmaceuticals. Together with Nele Van Dessel, a bioengineer and co-developer of the bacterial delivery system, the team has refined the platform to enhance safety and efficacy.
"Our goal is to unlock new possibilities for treating late-stage cancers," says Raman. "This approach leverages bacteria's natural ability to home to tumors, making it both highly targeted and patient-friendly."
How BacID Works
BacID is based on genetically engineered strains of Salmonella, modified to target tumors and release cancer therapies directly inside cancer cells. Key features of the therapy include:
Enhanced Safety: The bacteria used in BacID are at least 100 times safer than previous generations, thanks to advanced genetic engineering.
Targeted Drug Delivery: BacID can deliver significantly higher doses of therapeutic agents directly into tumors, sparing healthy tissue and minimizing side effects.
Controlled Activation: The bacteria’s therapeutic function is activated using a simple dose of aspirin. Without this activation, the bacteria remain dormant within tumors, further enhancing safety.
Innovative Mechanisms of Action
The BacID platform incorporates two revolutionary mechanisms:
Controlled Flagella Activation: Bacterial flagella, essential for tumor cell invasion, are produced only when activated by salicylic acid—the active metabolite of aspirin. This ensures precise targeting and minimizes the risk of unintended interactions with healthy cells.
Suicide Circuit: Once inside cancer cells, the bacteria self-rupture, effectively delivering the therapeutic agents directly where they are needed.
Pre-Clinical Success
In mouse models, BacID has demonstrated remarkable precision and efficacy:
Following intravenous injection, the attenuated bacteria are rapidly cleared from healthy tissues within two days.
The bacteria continue to grow exponentially only within tumors.
On the third day, a simple oral dose of aspirin activates the bacteria to invade cancer cells and deliver the therapy.
Toward Clinical Trials
The team is now focusing on the regulatory approval process to begin clinical trials. "We’ve designed this treatment to be as straightforward as possible," says Raman. "A patient could receive the infusion and, three days later, take an aspirin at home to complete the therapy."
A New Frontier in Cancer Treatment
With this innovative approach, BacID represents a significant advancement in microbial-based cancer therapies. "This technology has the potential to revolutionize how we treat high-mortality cancers," adds Raman. "We are proud to lead the way in this emerging field."
Reference
Vishnu Raman, Christopher L. Hall, Victoria E. Wetherby, Samantha A. Witney, Nele Van Dessel, Neil S. Forbes. Controlling intracellular protein delivery, tumor colonization and tissue distribution using the master regulator flhDC in a clinically relevant ΔsseJ Salmonella strain. Molecular Therapy, 2024; DOI: 10.1016/j.ymthe.2024.12.038
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