Bioengineered approach shows promise in ulcerative colitis: Newsroom – UT Southwestern, Dallas, Texas – UT Southwestern

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DALLAS Jan. 16, 2024 By taking advantage of mechanisms that allow cancer cells to evade immune attack, UTSouthwestern Medical Center researchers have developed a new strategy in animal models that has potential for treating ulcerative colitis. Their findings, reported in Nature Biomedical Engineering, could eventually provide relief to millions of people worldwide who have this or other autoimmune conditions.

Were 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 the Harold C. Simmons Comprehensive Cancer Center at UTSouthwestern. Dr. Wang co-led the study with first author Kin Man Au, Ph.D., Assistant Professor of Radiation Oncology.

Andrew Wang, M.D., Professor and Vice Chair of Translational Research and Commercialization in the Department of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UTSouthwestern, holds the A. Kenneth Pye Professorship in Cancer Research.

For decades, Dr. Wang explained, researchers have known that the immune system can recognize and kill cancers, keeping most malignancies in check. However, cancers can develop the ability to escape the immune system, producing proteins in their microenvironment that suppress immune cell activity and allow tumors to flourish. Conversely, autoimmune conditions develop when the immune system mistakes healthy cells as foreign invaders and launches unnecessary immune attacks.

Dr. Wang and his colleagues realized that they could take a page from cancers playbook, 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 colon cells. For this and other autoimmune diseases, there is no cure. These conditions are typically treated with systemic immunosuppressors, 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 heavy intestinal inflammation and damage suffered by human patients. Drs. Wang and Au and their colleagues injected the animals with a mixture of colon cells and the extracellular matrix that typically surrounds them simulating the tissue typically attacked in ulcerative colitis along with polymer nanofibers chemically altered to carry a variety of proteins and other molecules that cancer cells use to suppress immune activity.

Kin Man Au, Ph.D., Assistant Professor of Radiation Oncology, is the study's first author.

These injections not only significantly reduced symptoms of ulcerative colitis, such as diarrhea, rectal bleeding, weight loss, and inflammation-associated colon shortening, but tissue analysis showed that this treatment also reduced immune cell infiltration into the colons lining and its concentration of inflammatory molecules. Within seven days after injection, researchers saw that the colons lining appeared completely healed in mice that received the combination. Those treated with only parts of the combination or no injection at all still had actively inflamed colon lesions, the study showed.

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

Dr. Wang holds the A. Kenneth Pye Professorship in Cancer Research.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty members have received six Nobel Prizes and include 26 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

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Bioengineered approach shows promise in ulcerative colitis: Newsroom - UT Southwestern, Dallas, Texas - UT Southwestern