Grant: Project Grant

Immunotherapy represents a major breakthrough in the battle against cancer as a relatively new form of precision medicine. While it has helped many people with lung cancer live longer, about half of patients still do not respond well to this treatment. We recently discovered that the gut microbiome influences the clinical response of patients undergoing immunotherapy treatment. To enhance immunotherapy efficacy, several strategies are being explored in clinical trials to shift and improve the microbiome composition. One approach being tested is called fecal microbiota transplantation (FMT), where stool from donor is given to patients to help rebalance their gut bacteria. While promising, this approach faces two major challenges: it is difficult to scale due to donor shortages and it has safety concerns. Our team studied data from multiple clinical trials, including one focused on non-small cell lung cancer, a type of lung cancer, and found that the key is not how many bacteria are added from the donor, but rather which harmful bacteria are removed after FMT. Certain immune proteins (called IgG antibodies) seem to target and clear out these harmful bacteria. This suggests a new connection between the immune system and gut health. Based on these insights, we are developing a new type of treatment using live biotherapeutic products (LBP), designed to safely trigger this beneficial shift without needing donor stool. We will use cultivated bacteria isolated from the donors and the patients in order to develop candidate LBP that will then be evaluated using different strategies. In parallel, we will continue to study the immune response to further understand how FMT can eliminate harmful bacteria. This could lead to personalized, immune-guided therapies, which improve cancer treatment outcomes and overcome the limitations of FMT.