Ulcerative Colitis Treatment: Bioengineered Breakthrough

Researchers at UT Southwestern Medical Center have devised a new technique in animal models for treating ulcerative colitis by exploiting systems that allow cancer cells to elude immune attacks. Their results, published in Nature Biomedical Engineering, have the potential to help millions of individuals worldwide suffering from this or other autoimmune disorders.

“We’re borrowing something that cancer uses for evil and making it into something good,” said senior author Andrew Wang, M.D., Professor and Vice Chair of Translational Research and Commercialization in the Department of Radiation Oncology and a member of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center. Dr. Wang co-directed the study with first author Kin Man Au, Ph.D., an Assistant Professor of Radiation Oncology.

For decades, Dr. Wang explained, researchers have known that the immune system can recognize and kill tumors, keeping most malignancies in check. Cancer cells, on the other hand, can gain the ability to evade the immune system by generating proteins in their microenvironment that decrease immune cell activity and allow tumors to thrive. Autoimmune diseases occur when the immune system misidentifies healthy cells as foreign invaders and initiates needless immunological responses.

Dr. Wang and his colleagues recognized they could mimic cancer’s strategy by retraining the immune system to limit action against certain cell types targeted in autoimmune illnesses. Previous research has used this method in animal models of Type 1 diabetes and multiple sclerosis.

This new study focuses on ulcerative colitis, a chronic condition caused by an immunological attack on colon cells. There is currently no cure for this or any other autoimmune condition. These disorders are usually treated with systemic immunosuppressants, which can lower excessive immunological activation. However, they have long-term health consequences, including a higher risk of infections and cancer.

The researchers used a well-established mouse model of ulcerative colitis, which replicates the severe intestine inflammation and damage experienced by human patients. Drs. Wang and Au, along with their colleagues, injected the animals with a mixture of colon cells and the extracellular matrix that normally surrounds them, simulating the tissue that is typically attacked in ulcerative colitis, as well as polymer nanofibers chemically altered to carry a variety of proteins and other molecules that cancer cells use to suppress immune activity.

These injections not only significantly reduced ulcerative colitis symptoms such as diarrhea, rectal bleeding, weight loss, and inflammation-associated colon shortening, but tissue analysis also revealed that this treatment reduced immune cell infiltration into the colon lining as well as the concentration of inflammatory molecules. Within seven days of injection, researchers discovered that the colon’s lining had entirely recovered in mice given the mixture. The study found that those who received only a portion of the combination or no injection at all had actively inflammatory colon lesions.

The medication significantly reduced the number of malignant colon tumors by 60% (both animal models and human ulcerative colitis patients are at higher risk for colon cancer). Furthermore, the injections appeared to focus just immunological activity against the colon and did not reduce immunity across the body. When the researchers administered injections to mouse models of ulcerative colitis that also carried melanoma and colon cancers, the animals reacted to immunotherapy for their cancer, which would not have been possible if they were systemically immunosuppressed.

Together, Dr. Wang said, these findings suggest that the combination injections could be a viable new way of treating ulcerative colitis. A similar approach may also be used to treat other autoimmune diseases. He and his colleagues have filed a patent to develop this strategy into a clinical treatment.