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A research team from the University of Massachusetts Amherst, in collaboration with Ernest Pharmaceuticals, has developed a novel bacterial therapy, BacID, designed to deliver cancer-fighting drugs directly to tumors. This treatment promises a safer, more targeted approach to combating cancers with high mortality rates, such as liver, ovarian, and metastatic breast cancers by using genetically engineered Salmonella. Clinical trials involving patients are anticipated to start in 2027, according to the researchers.
A Decade of Innovation in Bacterial Therapies
The findings, recently published in Molecular Therapy, mark the culmination of over ten years of research by Neil Forbes, a chemical engineering professor at UMass Amherst, and Vishnu Raman, lead author and chief scientific officer at Ernest Pharmaceuticals. The technology relies on the natural ability of bacteria to home in on tumors, while genetic engineering ensures precise drug delivery and improved safety.
“What we’re trying to do is unlock the potential to treat late-stage cancers,” Raman explained. “Because this treatment is so targeted, it can address certain cancers without the harsh side effects seen with systemic therapies like chemotherapy.”
Controlled Targeting and Activation
The BacID platform introduces two key innovations. First, the bacteria's ability to invade cancer cells is controlled by a genetic circuit activated by aspirin, a widely available drug. The bacteria remain dormant in the tumor until the patient takes an aspirin dose, triggering the production of flagella—appendages that enable bacterial movement and cell invasion. Second, once the bacteria invade the cancer cells, they self-destruct, releasing the therapeutic payload directly inside the cells. This suicide mechanism minimizes risks to surrounding healthy tissue.
“We were focusing on how to make this strain really safe and user-friendly,” Raman stated. “The genetic engineering steps we took made this strain at least 100 times safer than anything that’s been tried in the past.”
Preclinical Success in Mouse Models
In preclinical studies using mouse models, the bacteria were injected intravenously. While they initially spread throughout the body, the immune system cleared them from healthy tissues within two days. By the third day, the bacteria concentrated within tumors. At this point, a dose of aspirin activated the bacteria to invade cancer cells and deliver the therapy. “We wanted to make it as simple as possible,” Raman emphasized. “So, the patient could get the infusion and three days later, at home, they just take an oral dose of aspirin.”
Looking Ahead to Clinical Trials
The team is now working on securing regulatory approval to initiate clinical trials. The potential of microbial therapies has been steadily gaining attention in cancer research. “We have seen a lot of growth in the area of microbial-based cancer treatment,” Raman shared, “and we are proud to be at the forefront of this field.”
Publication Details
Raman V, Hall CL, Wetherby VE, Witney SA, Van Dessel N, Forbes NS. Controlling intracellular protein delivery, tumor colonization and tissue distribution using the master regulator flhDC in a clinically relevant ΔsseJ Salmonella strain. Molecular Therapy. Published online January 17, 2025. doi:10.1016/j.ymthe.2024.12.038.
A Decade of Innovation in Bacterial Therapies
The findings, recently published in Molecular Therapy, mark the culmination of over ten years of research by Neil Forbes, a chemical engineering professor at UMass Amherst, and Vishnu Raman, lead author and chief scientific officer at Ernest Pharmaceuticals. The technology relies on the natural ability of bacteria to home in on tumors, while genetic engineering ensures precise drug delivery and improved safety.
“What we’re trying to do is unlock the potential to treat late-stage cancers,” Raman explained. “Because this treatment is so targeted, it can address certain cancers without the harsh side effects seen with systemic therapies like chemotherapy.”
Controlled Targeting and Activation
The BacID platform introduces two key innovations. First, the bacteria's ability to invade cancer cells is controlled by a genetic circuit activated by aspirin, a widely available drug. The bacteria remain dormant in the tumor until the patient takes an aspirin dose, triggering the production of flagella—appendages that enable bacterial movement and cell invasion. Second, once the bacteria invade the cancer cells, they self-destruct, releasing the therapeutic payload directly inside the cells. This suicide mechanism minimizes risks to surrounding healthy tissue.
“We were focusing on how to make this strain really safe and user-friendly,” Raman stated. “The genetic engineering steps we took made this strain at least 100 times safer than anything that’s been tried in the past.”
Preclinical Success in Mouse Models
In preclinical studies using mouse models, the bacteria were injected intravenously. While they initially spread throughout the body, the immune system cleared them from healthy tissues within two days. By the third day, the bacteria concentrated within tumors. At this point, a dose of aspirin activated the bacteria to invade cancer cells and deliver the therapy. “We wanted to make it as simple as possible,” Raman emphasized. “So, the patient could get the infusion and three days later, at home, they just take an oral dose of aspirin.”
Looking Ahead to Clinical Trials
The team is now working on securing regulatory approval to initiate clinical trials. The potential of microbial therapies has been steadily gaining attention in cancer research. “We have seen a lot of growth in the area of microbial-based cancer treatment,” Raman shared, “and we are proud to be at the forefront of this field.”
Publication Details
Raman V, Hall CL, Wetherby VE, Witney SA, Van Dessel N, Forbes NS. Controlling intracellular protein delivery, tumor colonization and tissue distribution using the master regulator flhDC in a clinically relevant ΔsseJ Salmonella strain. Molecular Therapy. Published online January 17, 2025. doi:10.1016/j.ymthe.2024.12.038.