September 20, 2024

By: Toni Shears

 

Every day, the human immune system is quietly working miracles in our bodies, maintaining health and curing illness. But when the immune system is overwhelmed — or when it goes into overdrive and attacks healthy tissues — we are plagued with disease. 

 

Much of modern medicine focuses on leveraging and amplifying the natural powers of the immune system. The College of Pharmacy’s James Moon is working at the cutting edge of this field, deploying the sophisticated tools of drug delivery technologies, biomaterials and more to improve immune functions. His wide-ranging work offers hope for treating various diseases, including cancer, autoimmune diseases like multiple sclerosis, and chronic conditions like allergies. 

 

A Platform for Anti-Cancer Vaccines

In his early work when he joined the CoP faculty in 2012, in collaboration with Dr. Anna Schwendeman Moon developed nanodiscs designed to deliver anti-cancer vaccines directly to immune cells. The nanodiscs, engineered from lipoproteins, can be linked to peptides and directed to the lymph nodes, where the dendritic cells that spark an immune response are found in abundance.

 

“These nanodiscs are novel drug delivery systems that can deliver a payload to immune and tumor cells to enhance the immune response against cancer,” says Moon, the J. G. Searle Professor of Pharmaceutical Sciences. “Once you attach peptides and inject these particles under the skin, they go very efficiently to the lymph nodes, where they need to be to trigger an immune response.”  

 

A 2020 paper that Moon co-authored shows that these nanodiscs elicit a strong T cell response, and the T cells successfully infiltrate tumors in mice. “These nanodiscs are small, scalable, and versatile, making them an effective cancer vaccine platform,” says Moon, who also holds professorships in biological and chemical engineering at the University of Michigan College of Engineering.

 

Nanodiscs can be engineered for patient-specific therapies and aimed at specific targets at play in many different diseases. For instance, the use of synthetic lipoproteins as a carrier to deliver beneficial agents has been tested as a treatment for other conditions like vascular disease and aneurysms. 

 

Targeting the Gut Microbiome

Another line of Moon’s research involves stimulating the gut biome to fight disease. Recent studies have revealed that the millions of bacteria in our gastrointestinal tract play a vital role in our health. Every individual has a unique set of microbes making up their gut biome, and imbalances can impact the heart, the brain, and immune responses. Moon has seized on this as a new target for immunotherapy. 

 

His team found a way to transform a polysaccharide called inulin into a gel that coats the walls of the GI tract. Found in plants like chicory and Jerusalem artichoke and sometimes used as a sugar substitute, this polysaccharide serves as a nutrient source for bacteria in the gut. The gel can rebalance the bacteria in the gut.

 

This inulin gel can also feed and fuel helpful bacteria in the gastrointestinal tract, supercharging their cancer-fighting properties. When fed with inulin, these bacteria multiply and increase the production of beneficial compounds called short-chain fatty-acid metabolites. These, in turn, act as a powerful tumor suppressor. Moon’s research shows that this results in significant tumor suppression and reduction in mice.

 

Inulin, a widely consumed, FDA-approved dietary fiber “shows promise as a very safe way to improve the gut microbiome to treat cancer,” Moon says. A recent healthy volunteer study has indicated that inulin gel given as an oral 20-gram daily serving is well tolerated without major complications.  

 

It offers potential for stimulating the gut microbiome to address other conditions beyond cancer. “We can design prebiotics to deliver to the GI tract that are aimed to carry useful compounds and drugs to the right site of action,” Moon notes.

 

Suppressing Food Allergies

Inulin gel also shows promise for suppressing food allergies that affect millions. In a new breakthrough reported in Nature Materials, Moon’s research in mice shows that the gel can reduce the anaphylaxis response to peanut as well as milk allergies. 

 

When formulated with food allergens, the inulin gel normalized the imbalance of microbes and metabolites in the intestines of allergic mice and suppressed allergic reactions to various food allergens, including peanuts and milk. 

 

This gel-based immunotherapy not only reduces allergy symptoms but addresses the underlying cause. It restores beneficial bacteria in the gut associated with food allergy regulation, correcting the imbalances associated with food allergies. As a result, treated mice developed a tolerance for the allergen.

 

Food allergies are increasingly prevalent. Plant-based, inexpensive, and easily tolerated, inulin gel formulation may offer a safeguard for the millions of those who are at risk of severe and dangerous allergic reactions. Moon and his colleagues are aiming to evaluate inulin gel in patients in the near future. 

 

Leveraging Natural Therapies. 

All these different lines of research are based on highly advanced pharmaceutical sciences — yet their effectiveness may arise from exploiting natural products and processes. Nanodiscs are made from a form of fat, engineered to carry useful peptides or other molecules to target cells. They can be structured to initiate or modulate an immune response. Likewise, immunotherapy aimed at the gut microbiome is designed to correct or enhance natural processes with healing impact.

 

Early work shows promise for treating devastating diseases like cancer and food allergies and offers hope for millions, showing the potential of powerful discoveries still to come.