Lee, Young form multidiscipline collaboration to investigate micro-cytokine factories

Associate professors Chun-Teh Lee, DDS, DMSc, MS, and Simon Young, DDS, MD, PhD, of UTHealth Houston School of Dentistry are serving as investigators on two federal grants totaling almost $1 million from the National Institute of Dental and Craniofacial Research to investigate a novel micro-cytokine factory platform for the treatment of periodontal disease and oral cancer.

The researchers note the role cytokines play in immune cells to either ramp up or turn down the immune response. To this end, they aim to test localized cytokine delivery across two dental applications — the treatment of periodontal disease and oral cancer.

In treating a patient with periodontal disease, a provider looks to “turn down” the inflammation, whereas in an oral cancer patient, the immune response needs to be “turned up” against the tumor.

They propose to place cytokines locally — in known regions where periodontal disease or oral cancer occurs to avoid the toxic, systemic side effects commonly associated with these potent drugs.

Lee, as the principal investigator for “Engineered Cytokine-Secreting Bacteria to Treat Periodontitis,” hypothesizes that localized and sustained delivery of the anti-inflammatory cytokine, interleukin-10 (known as IL-10), from well-contained Limosilactobacillus reuteri (L. reuteri) can reduce periodontal inflammation and promote periodontal tissue healing.

“We hope to demonstrate that localized host modulation through the biomaterial-based application of engineered L. reuteri can treat experimental periodontitis,” Lee said. “This will shed light on novel clinical applications of engineered microorganisms able to achieve localized, sustained host modulation in treating periodontitis using a combinatorial strategy of biomaterials and synthetic biology.”

For Young, the principal investigator for “Engineered Bacterial in Situ Vaccines against Oral Cancer,” his goal is to achieve localized and controlled delivery of the immunostimulatory cytokines, interleukin-12 (IL-12) targeting the immune microenvironment and tumor-draining lymph nodes after tumor resection surgery. The goal is to produce robust anti-tumor responses that eliminate both local tumor recurrence and lymph node metastases.

“For thousands of years, surgery has been the fundamental treatment modality for solid tumors,” Young said. “Innovations in radiation therapy and chemotherapy contributed to improved patient outcomes in the 20th century. More recently, immunotherapy has emerged as an exciting additional ‘pillar’ of cancer therapy, but the traditional systemic method of delivery can have serious immune-related side effects, even death. We’re very excited about working with our colleagues at Rice on these implantable, living micro-cytokine factories because they can deliver very potent cytokines in a localized fashion for an extended amount of time.

“Our plan is to implant them into the resection cavity after a tumor undergoes standard-of-care surgical removal. This will theoretically allow the ‘cancer vaccine’ to continuously stimulate the immune system in a safe and effective way to clean up residual cancer cells left behind and prevent them from spreading.”

Lee and Young hope to gather preliminary data on these separate applications of this novel micro-cytokine factory platform to present for future grant proposals.

The two UTHealth Houston School of Dentistry researchers have paired with Rice University’s Omid Veiseh, PhD, who will serve as lead on biomaterials and encapsulation, and Jeffrey Tabor, PhD, who will oversee bacteria programming, to assist with these grants.

The R21 grants will be awarded over a two-year span through August and September 2026, respectively.