ChE’s Neil Forbes and Colleagues Engineer Pioneering Bacterial Treatment for High-mortality Cancers

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A team of University of Massachusetts Amherst-Ernest Pharmaceuticals scientists, led by Professor Neil Forbes of the Chemical Engineering (ChE) Department, has made groundbreaking advances in engineering a non-toxic bacterial therapy to deliver cancer-fighting drugs directly into tumors. This emerging technology promises very safe and effective treatment of cancers with high mortality rates, including liver, ovarian, pancreatic, and metastatic-breast malignancies. The UMass News Office recently covered this trailblazing research in an illuminating article (https://www.umass.edu/news/article/research-using-non-toxic-bacteria-fight-high-mortality-cancers-prepares-clinical).

The News Office article explains that clinical trials with participating cancer patients are estimated to begin in 2027. “This is exciting because we now have all the critical pieces for getting an effective bacterial treatment for cancer,” says Forbes, principal investigator of the research described recently in the journal Molecular Therapy.

Forbes has been working for more than two decades with what he calls “super-safe Salmonella bacteria” to act as Trojan Horses that deliver cancer-killing agents directly into tumors. These meticulously engineered Salmonella can use their own self-propulsion system of flagella to venture deep into tumors and deliver cancer-destroying agents, all without causing the vicious side effects of many chemotherapy treatments.

In the past, Forbes has said that his Salmonella vectors are designed to steal into cancer tumors, interrupt essential cell processes there, destroy cancer cells, eliminate cancer stems cells, reduce tumor volume, and block the formation of metastases. 

As the Molecular Therapy paper explains, “Effectively targeting intracellular pathways in cancers requires a system that specifically delivers to tumors and internalizes into cancer cells. To achieve this goal, we developed intracellular-delivering Salmonella with controllable expression of flhDC [a protein complex] to regulate flagella production and cell invasion. We hypothesized that controlling flhDC would overcome the poor [tumor] colonization seen in prior clinical trials.”

As the Molecular Therapy paper notes, “This clinically ready strain preferentially colonized metastatic breast tissue 280 and 800 times more than surrounding healthy tissue in the lung and liver, respectively. By precisely controlling tumor colonization and cell invasion, this strain overcomes critical limitations of bacterial therapy and will enable treatment of many hard-to-treat cancers.”

According to Vishnu Raman, who earned his Ph.D. in the Forbes Lab and was the lead author of the Molecular Therapy paper, “What we’re trying to do is unlock the potential to treat late-stage cancers. Bacteria naturally home to tumors, and this treatment is so targeted, it can treat some cancers without the harsh side effects you’d see with other systematically delivered therapies, like chemotherapy.”

The new findings are the culmination of more than a decade of research by Raman, a chief scientific officer at Ernest Pharmaceuticals, a company co-founded by Raman, Forbes, and Molecular Therapy paper co-author Nele Van Dessel. She is a bioengineer who helped develop the bacterial-delivery system as a post-doctoral researcher in the Forbes Lab and is currently also a chief scientific officer at Ernest Pharmaceuticals.

According to the New Office story, the team has been finetuning the development of these non-toxic, genetically engineered strains of Salmonella to target tumors and then control the release of cancer-fighting drugs inside cancer cells. In addition to sparing healthy tissue from damage, this cancer-treatment platform can deliver orders-of-magnitude more therapy than the administered dose because these simple-to-manufacture bacteria grow exponentially in tumors once they colonize them. 

“We were focusing on how to make this strain really safe and user-friendly,” Raman says. “The genetic-engineering steps we took made this strain at least 100 times safer than anything that’s been tried in the past.” (March 2025)