Join us for the next Bioengineering Department Seminar:
Wednesday, December 4
12noon – 1:00pm
Stanley Hall, Room 106
“Engineering Strategies to Modulate the Gut Microbiome and Immune System”
Dr. James Moon
J. G. Searle Professor
Departments of Pharmaceutical Sciences,
Biomedical Engineering and Chemical Engineering
University of Michigan
Abstract:
New approaches are needed to improve immunotherapies with minimal immune-related adverse events. The gut microbiome has recently emerged as the next frontier in drug development; however, it remains unclear how to effectively alter gut microbiota for treating various diseases, including cancer. Here, we present new biomaterial-based strategies for altering the gut microbiome and improving the safety and efficacy of 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 administration of inulin-gel in tumor-bearing mice in combination with anti-PD-1 immune checkpoint blockade led to robust anti-tumor efficacy while mitigating immune-related adverse events. In our second research thrust, we are developing a new nanoparticle platform for systemic delivery of STING (stimulator of IFN genes) agonists. While local STING activation can convert cold tumor into hot tumor, it has been challenging to develop STING agonists that can treat disseminated cancer due to their toxicity. Here, we will present our data showing that addition of manganese to STING agonists results in robust synergy. Lipid-based nanoparticles containing manganese and STING agonists allows for systemic cancer immunotherapy with potent efficacy, favorable pharmaceutical properties, and acceptable safety profiles in various murine and rabbit tumor models. Our biomaterial-based strategies may offer powerful and convenient approaches to regulate the immune system as potential therapies for cancer and other diseases.