Engineering Strategies to Modulate the Immune System
Abstract
Advancing immunotherapy necessitates novel strategies that enhance therapeutic efficacy while minimizing immune-related adverse events. Among emerging frontiers, the gut microbiota—a complex and dynamic microbial ecosystem predominantly residing in the colon—has garnered intense scientific interest. The gut microbiome plays a pivotal role in modulating host immunity, and its dysbiosis is associated with a spectrum of diseases, underscoring the urgent need for targeted interventions. Here, we present a new strategy to modulate the gut microbiota for improving cancer immunotherapy. We are developing new dietary fiber-based biomaterials for in situ modulation of the gut microbiome for augmenting local and systemic immune responses. Oral inulin-gel enriches beneficial taxa through microbial fermentation, boosting both local and systemic immune activation. In tumor-bearing mice, inulin-gel in combination with anti-PD-1 immune checkpoint blockade led to robust anti-tumor efficacy while mitigating immune-related adverse events. Our gut microbiome-modulation strategies are currently being evaluated in clinical trials. As our second research thrust, we are developing a novel systemic delivery system for STING (stimulator of interferon genes) agonists, a critical pathway for orchestrating immune responses against cancer. While local STING activation effectively converts "cold" tumors into immunologically "hot" tumors, systemic delivery has been hampered by toxicity challenges. To overcome these challenges, we are developing lipid-based nanoparticles containing manganese and STING agonists as a potent platform for cancer immunotherapy. These nanoparticles demonstrate robust anti-tumor efficacy across various preclinical cancer models with a favorable safety profile. Our biomaterial-based strategies may offer powerful and convenient approaches to regulate the immune system as potential therapies for cancer and other diseases.
Bio
Dr. James Moon is John Gideon Searle Professor in the Department of Pharmaceutical Sciences, Biomedical Engineering, and Chemical Engineering at the University of Michigan, Ann Arbor. His interdisciplinary research program aims to develop novel biomaterials-based strategies to advance fundamental understanding of the immune system, with the ultimate goal of improving patients’ lives with effective vaccines and immunotherapies. Dr. Moon has published over 130 research articles, including those published in Nature Materials, Nature Medicine, Nature Nanotechnology, and Nature Biomedical Engineering. He has over 27 pending/approved U.S. and international patent applications, and his novel nano-vaccine delivery technologies have led to 3 new start-up companies, including EVOQ Therapeutics and Saros Therapeutics. Dr. Moon is a fellow of Biomedical Engineering Society (BMES), American Institute for Medical Biological Engineering (AIBME), and Controlled Release Society (CRS), and his contributions to the field has been recognized with numerous awards, including NSF CAREER Award and Samyang CRS Award. Dr. Moon received his bachelor’s degree from the University of California, Berkeley (2002), and his Ph.D. from Rice University (2008), and he completed his postdoctoral training at MIT. He joined the faculty of the University of Michigan in 2012.