Cancer-fighting bacterial product ‘cocktails’ may offer personalized treatment

UNIVERSITY PARK, Pa. — Bacteria may be the next frontier in cancer treatment, according to a team led by researchers at Penn State that devised a new approach of creating bacteria-derived mixtures — or cocktails — to help fight bladder cancer. They tested their mixtures of good and bad bacteria on patient tumor samples and in mice, finding that the cocktails significantly boost the immune system’s ability to fight cancer. 

The researchers explained how the approach, detailed in a paper published today (Dec. 2) in Nature Communications, could be personalized to a patient's specific health needs, while delivering more efficient treatment at a cost comparable to, or lower than, existing cancer treatment options. 

According to lead author Pak Kin Wong, professor of biomedical engineering and of mechanical engineering at Penn State, one of the most promising approaches to treating cancer is immunotherapy, where doctors use a patient's immune system to target cancer cells. In bladder cancer, doctors can introduce live bacteria into a patient’s body to engage their immune system in the fight against cancerous cells. This approach, called bacillus Calmette–Guérin (BCG) immunotherapy, was originally reported in the 1976 and is still the only approved method of bacterial immunotherapy for use in the clinic, Wong said. Despite its singular status, Wong explained it still has much room for optimization.

“People have recognized the connection between bacterial infection and cancer regression since the 1800s,” Wong said, noting that it still took more than a century for that understanding to transform into an actual treatment with BCG. “However, this type of immunotherapy, which relies on a single bacterial type, works for only a portion of patients. We now know that our immune system interacts with thousands of different kinds of bacteria every day, which opens many new possibilities and can help make treatments more effective.” 

The new approach, which the team calls microbial product cocktail (MPC) immunotherapy, uses microbial products derived from bacteria instead of the live, whole bacteria used in BCG immunotherapy. Wong explained how using these products allows researchers to have more control during treatment and, in turn, test more bacterial mixtures without the risk of harmful bacteria making patients sick. To decide the specific mixtures of products used, the researchers developed an artificial intelligence (AI) model that optimizes both the composition and relative dosage of microbial products, testing these AI-optimized cocktails in tumor organoids — mini-tumors derived from a patient’s tumor tissues — to evaluate how well each cocktail activated the patient’s immune response. This approach allows the MPC immunotherapy to be personalized for each individual patient.

According to Wong, this approach to MPC immunotherapy was previously challenging due to the sheer number of possible bacterial combinations. By integrating AI into the process, the team can now predict which microbial product cocktails are most likely to be effective and select the best candidates for testing in each patient’s organoid.

“By running a small set of tests on the organoids in the lab, we can see how well a patient’s tumor draws in immune cells, whether it behaves like an inflamed, or hot, tumor and which cocktail works best for them,” Wong said. “Using this information, our system can quickly point to the most effective treatment.”

To verify their findings, the team tested their cocktails in mice with bladder cancer, a traditional way of testing preclinical immunotherapy treatments. The approach more than doubled long-term cancer survival rates when compared to BCG immunotherapy, according to Wong. Additionally, mice treated with the MPC method showcased an increased presence of cancer-fighting immune cells, demonstrating how personalized cocktails improved the defensive immune response to cancer compared to mice treated with BCG immunotherapy.

Looking forward, the team plans to continue developing their technique and expand it to other cancer types. Although the treatment only targets bladder cancer currently, Wong explained that this approach to immunotherapy could potentially be adapted to treat various other types of cancer.

“We’re just at the beginning of what this approach can do,” Wong said. “As we continue development, we will better understand how the immune system interacts with bacteria and how we can use it to combat cancer. Our hope is that this approach will eventually become a go-to option for efficient, safe and personalized cancer treatment.”

Other Penn State co-authors include Yue Yan, who recently received her doctorate in bioengineering and biomedical engineering; Sijia Yang, a biomedical engineering doctoral candidate; Guoli Chen, associate professor of pathology and laboratory medicine at the Penn State College of Medicine; and David J. DeGraff, associate professor of urology in the Penn State College of Medicine. Additional co-authors include Kathleen E. Mach, a senior research scientist at the Stanford University School of Medicine; and Joseph C. Liao, professor of urology at Stanford University School of Medicine.

This research was supported by the U.S. National Science Foundation and National Institutes of Health. 

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