A scientist at Weill Cornell Medicine is working with colleagues at the University of Massachusetts Amherst on new, complementary research efforts engineering therapeutic Salmonella to target critical gaps in treatment for drug-resistant triple-negative breast cancers. The team has received a five-year, $13.1 million grant, the first of its kind for bacteria cancer therapies awarded by the U.S. National Institutes of Health, to support research to design nontoxic bacteria strains that can deliver three treatment options.
Dr. Sarah Cheal, an assistant professor of biological chemistry in radiology at Weill Cornell Medicine and a multiple project investigator on the grant, will receive $2.7 million of the funding to use the 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 other efforts include using genetically engineered bacteria to "decorate" cancer with a COVID-derived protein, essentially tricking the immune system into recognizing and attacking a tumor; building on previous research to kill cancer cells with viruses-delivered by Salmonella-instead of with drugs, to address the challenge of tumors evolving to resist treatment; creating a massive library of Salmonella genetics to enable the precise tailoring of the bacteria to serve as vehicles for different therapies; and refining light-emitting molecules to study real-time behavior of immune cells in response to the various Salmonella-based treatments.
Dr. Cheal, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell, is working with UMass Amherst investigators Dr. Neil Forbes, a professor of chemical and biomolecular engineering; Dr. Lisa M. Minter, professor of veterinary and animal sciences; Dr. Lauren Andrews, associate professor of chemical and biomolecular engineering; Dr. Ashish Kulkarni, professor of chemical and biomolecular engineering; and Dr. Joseph Jerry, professor emeritus of veterinary and animal sciences.
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