Scientists have achieved significant and promising advancements in creating a non-toxic bacterial therapy called BacID, designed to deliver cancer-fighting drugs directly into tumors. This innovative approach shows great potential for providing safer and more effective treatments for aggressive cancers that pose high risks to patients, such as liver, ovarian, and metastatic breast cancer.
Researchers from a partnership between the University of Massachusetts Amherst and Ernest Pharmaceuticals have made noteworthy advancements in developing BacID, a non-toxic bacterial therapy that administers cancer-fighting drugs directly to tumors. This innovative technology offers hope for safer and more efficient treatment options for cancers with high mortality rates, like liver, ovarian, and metastatic breast cancer.
Clinical trials involving cancer patients are expected to commence in 2027. “This is an exhilarating development because we now possess all the essential components for a successful bacterial treatment for cancer,” comments Neil Forbes, the lead author of a study recently published in the journal Molecular Therapy and a professor of chemical engineering at UMass Amherst.
“Our goal is to unlock the potential for treating late-stage cancers,” explains lead author Vishnu Raman, who completed his Ph.D. in the Forbes Lab at the UMass Amherst Institute for Applied Life Sciences (IALS). “Bacteria naturally target tumors, and since this therapy is highly focused, it can treat certain cancers without the severe side effects commonly associated with other systemic treatments like chemotherapy.”
These new findings are the result of more than ten years of dedicated research by Raman, who serves as the chief scientific officer of Ernest Pharmaceuticals. This IALS startup was co-founded by Raman, Forbes, and co-author Nele Van Dessel, a bioengineer who created the bacterial delivery system as a post-doctoral researcher in the Forbes Lab.
The team has refined non-toxic, genetically modified strains of Salmonella to zero in on tumors, enabling controlled release of cancer-fighting drugs within cancer cells. This method not only protects healthy tissue from damage but also allows for a significantly higher dosage of therapy since the easy-to-manufacture bacteria multiply rapidly within tumors.
“Our focus was on ensuring that this strain remains very safe and user-friendly,” remarks Raman. “The genetic modifications made this strain at least 100 times safer than any previously tested options.”
In this upgraded delivery strain, Raman discovered a method to regulate when the bacteria invade cancer cells after being injected into the bloodstream. This enhancement allows for more precise targeting of tumors, resulting in higher concentrations of drug therapy and increased safety. “With the first-generation strain, we relied on the bacteria’s natural ability to locate tumors and deliver treatment, which came with risks like invading healthy cells or being cleared from the body before they could settle in tumors. We aimed to reduce both risks,” explains Raman.
During the initial stages of research, scientists found that bacterial flagella, which aid in movement, play a crucial role in the bacteria’s ability to invade cancer cells. Consequently, they engineered a genetic circuit that activates the production of flagella in the bacteria with a simple over-the-counter dose of aspirin. Without this activation, the bacteria remain inactive within the tumor.
“Controlling flagella activation is a key part of this technology,” Raman clarifies. “Additionally, once the bacteria enter cancer cells, we’ve equipped them with a self-destruct mechanism. This allows them to rupture and release the therapy inside the cancer cell.”
In pre-clinical trials using mouse models, the bacteria are introduced through intravenous injection. “They spread throughout the body, but the immune system quickly eliminates these weakened bacteria from healthy organs within two days. They continue to proliferate only within tumors during that period. On the third day, we administer an over-the-counter aspirin dose to prompt the bacteria to invade the cancer cells and deliver the treatment,” Raman shares.
“We’ve designed the process to be as straightforward as possible,” he adds. “This way, the patient can receive the infusion and just take an oral aspirin dose three days later at home.”
The team is currently working on securing the necessary approvals to initiate clinical trials.
“The field of microbial-based cancer treatments is experiencing rapid growth,” Raman states, “and we are proud to be leading the charge in this area.”
