Bioengineering approach shows promise in treating ulcerative colitis

By taking advantage of the mechanisms that allow cancer cells to evade immune attack, researchers at UT Southwestern Medical Center have developed a new strategy in animal models that could treat ulcerative colitis. Their conclusions, reported in Natural biomedical engineeringcould potentially bring relief to millions of people around the world who suffer from this or other autoimmune diseases.

“We’re borrowing something that cancer uses for bad and making it into something good,” said lead author Andrew Wang, MD, professor and vice chair of translational research and commercialization in the Department of Radiology. oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Wang co-led the study with first author Kin Man Au, Ph.D., assistant professor of radiation oncology.

For decades, Dr. Wang said, researchers have known that the immune system can recognize and kill cancers, thereby controlling most malignancies. However, cancers can develop the ability to evade the immune system, producing proteins in their microenvironment that suppress immune cell activity and allow tumors to grow. Conversely, autoimmune diseases develop when the immune system mistakes healthy cells for foreign invaders and launches unnecessary immune attacks.

Dr. Wang and his colleagues realized they could take a page from the cancer model, retraining the immune system to suppress its activity against specific cell types attacked in autoimmune diseases. Previous studies have used this approach in animal models of type 1 diabetes and multiple sclerosis.

This latest study focuses on ulcerative colitis, a chronic disease characterized by an autoimmune attack against cells in the colon. There is no cure for this and other autoimmune diseases. These conditions are usually treated with systemic immunosuppressants, which can reduce inappropriate immune activity. But they have long-term health complications, including an increased risk of infections and cancer.

The researchers worked with a well-established mouse model of ulcerative colitis that mimics the significant intestinal inflammation and damage experienced by human patients. Drs. Wang and Au and their colleagues injected animals with a mixture of cells from the colon and the extracellular matrix that typically surrounds them – simulating the tissue typically attacked in ulcerative colitis – along with chemically modified polymer nanofibers to carry a variety of proteins and other carcinogenic molecules. cells use to suppress immune activity.

Not only did these injections significantly reduce the symptoms of ulcerative colitis, such as diarrhea, rectal bleeding, weight loss, and shortening of the colon associated with inflammation, but tissue analysis showed that this Treatment also reduced the infiltration of immune cells into the colon mucosa and its concentration of inflammatory molecules. . Seven days after the injection, the researchers found that the colon lining appeared completely healed in the mice given the combination. According to the study, people treated with only parts of the combination or with no injection at all still had actively inflamed colon lesions.

The treatment also reduced the number of colon cancer tumors developed by 60% (both animal models and human patients with ulcerative colitis have an increased risk of colon cancer). Additionally, the injections appeared to only target immune activity against the colon and did not broadly suppress immunity in the body. When researchers gave injections to mouse models of ulcerative colitis that also had melanoma and colon tumors, these animals responded to immunotherapy for their cancer, which would not be possible if they were systemically immunocompromised.

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