Personalized Cancer Immunotherapy Delivered by Bacterial Cocktails Could Redefine Treatment
Bacteria may be the next frontier in cancer treatment. Researchers at Penn State have devised a new approach of creating bacteria‑derived mixtures—microbial product cocktails (MPCs)—to help fight bladder cancer. They tested their cocktails on patient tumor samples and in mice, finding that the mixtures significantly boost the immune system’s ability to fight cancer. The work, described in a paper published December 2 in Nature Communications, could be personalized to a patient’s health needs and delivered at a cost comparable to, or lower than, existing cancer treatments.
In This Article:
BCG Background: Live Bacteria versus Microbial Product Cocktails
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 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.”
AI‑Guided Personalization and Organoid Testing
The team’s approach, called 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. “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.”
Lab to Mice: Preclinical Proof of Concept
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 Ahead: Expanding Beyond Bladder Cancer
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.”
The Team, Co‑authors and Support
The research team, led by Pak Kin Wong, includes Yue Yan, Sijia Yang, Guoli Chen, and David J. DeGraff. Additional co‑authors include Kathleen E. Mach and Joseph C. Liao. This research was supported by the U.S. National Science Foundation and National Institutes of Health.
Federal Funding Context and the Path Forward
At Penn State, researchers are solving real problems that impact the health, safety and quality of life of people across the commonwealth, the nation and around the world. For decades, federal support for research has fueled innovation that makes our country safer, our industries more competitive and our economy stronger. Recent federal funding cuts threaten this progress. Learn more about the implications of federal funding cuts to our future at Research or Regress.
