UMass Amherst Leads $13.1M Research Effort to Treat Breast Cancer with Bacteria

Content

This story was first published by the UMass News Office.

Scientists at the University of Massachusetts Amherst have been awarded $13.1 million to lead new, complementary research efforts engineering therapeutic Salmonella to target critical gaps in treatment for drug-resistant triple-negative breast cancers. The five-year grant, the first of its kind for bacteria cancer therapies awarded by the U.S. National Institutes of Health, will support research to design nontoxic bacteria strains that can deliver three treatment options.

Neil Forbes, a professor in the Riccio College of Engineering at UMass Amherst and a member of the Center for Bioactive Delivery in the Institute for Applied Life Sciences (IALS), will oversee five interconnected research efforts that will tackle different ways breast cancer cells escape attack and further untangle the “whys” behind the science.

“What excites me is that engineered bacteria give us a way to image tumors and train a patient’s own immune system to find and eliminate them wherever they occur in the body,” says Forbes. “We look forward to generating several interrelated microbial therapies that will greatly improve the treatment of triple-negative breast cancer.”

In addition to overseeing the effort overall, Forbes will spearhead one of these projects. His work will be to push forward his research demonstrating that Salmonella can deliver viruses inside a tumor. The virus then replicates within cancerous cells, causing the tumor cells to split open and die.

The next project will use Salmonella to reveal tumors that are otherwise invisible to the immune system using a recall antigen. An antigen is found in routine vaccines and trains the immune system to recognize invaders. In this work, the Salmonella will carry the antigen to the tumor and “paint” it with proteins that the immune system has already been taught to seek and destroy, and, simultaneously, destroy the cancer.

The third project, taking place at Weill Cornell Medicine, aims to use this Salmonella delivery system for radiopharmaceutical therapy (RPT). RPT delivers radioactive metals directly to the tumor, causing less toxicity than traditional radiation. However, the issue is getting these radioactive metals to find the tumor. While the bacteria themselves cannot carry the radioactive metals, they can carry substances that attract the RPT, creating a homing beacon to the cancer-killing radioactivity.

Not only will this serve as a cancer therapy, but it can also be used for improved imaging, since the researchers will design Salmonella to carry metals that emit non-damaging beta radiation, called positrons, that can be seen from a positron emission tomography, or PET, scan.

The grant will also support the development of additional technologies that support these three projects and explain the underlying mechanics. This includes the creation of a massive library of Salmonella genetics. This will enable the researchers to tailor the Salmonella to perform the actions described in each project. Finally, the research will develop light-emitting molecules, called nanoreporters to study the real-time behavior of immune cells in response to the various Salmonella-based treatments.

“Doing these projects in parallel, instead of doing three separate projects, will be synergistic,” says Forbes. “As we understand mechanisms for one of the pieces, it’ll help us understand the others.”

“The work enabled by this award and by Ernest Pharmaceuticals—a start-up company co-founded by Forbes to develop therapeutics to develop bacterial cancer therapies—has the potential to establish highly differentiated and novel cancer treatments” added Peter Reinhart, director of IALS.

Joining Forbes are Lisa M. Minter, UMass professor of veterinary and animal sciences; Lauren Andrews, UMass associate professor of chemical and biomolecular engineering; Ashish Kulkarni, UMass professor of chemical and biomolecular engineering; Joseph Jerry, UMass professor emeritus of veterinary and animal sciences; and Sarah Cheal, assistant professor of biological chemistry in radiology at Weill Cornell Medicine.

While using bacteria to attack certain forms of cancer has been around for more than a century, Salmonella has become an attractive vehicle due to its ability to proliferate inside tumor microenvironments while delivering toxins to kill cancer cells.

“I wrote my first paper about this topic in 2001,” says Forbes, whose research has been published in journals including Nature Communications, Cell Reports Medicine and Frontiers in Immunology. “Recently, I found papers going back to the 1700s when people had been talking about it, before we even really knew what bacteria were. It’s old, but at the same time, it’s all new technology. There are things that we have not been able to do until fairly recently.”