By exploiting mechanisms that allow cancer cells to evade immune attack, UT Southwestern Medical Center researchers have developed a new strategy in animal models that has potential for treating ulcerative colitis. Their findings, reported in Nature Biomedical Engineeringit could ultimately provide relief to millions of people around the world who have this or other autoimmune conditions.
“We borrow something that cancer uses for evil and turn it into something goodsaid senior author Andrew Wang, MD, Professor and Vice Chair of Translational Research and Commercialization in the Department of Radiation Oncology and 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 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 evade the immune system by producing proteins in their microenvironment that suppress the activity of immune cells 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 the cancer playbook by retraining the immune system to suppress its activity against specific types of cells that are 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 the cells of the colon. For this and other autoimmune diseases, there is no cure. 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 an established mouse model of ulcerative colitis that mimics the severe intestinal inflammation and damage experienced by human patients. Drs. Wang and Au and their colleagues injected the animals with a mixture of colon cells and the extracellular matrix that normally surrounds them—simulating the tissue typically affected in ulcerative colitis—along with polymer nanofibers chemically altered to carry a variety of proteins and other molecules that cause cancer cells are used to suppress immune activity.
Not only did these injections significantly reduce symptoms of ulcerative colitis, such as diarrhea, rectal bleeding, weight loss, and inflammation-related shortening of the colon, but tissue analysis showed that this treatment also reduced the infiltration of immune cells into the lining of the colon and its concentration in inflammatory molecules. . Within seven days of the injection, the researchers saw that the lining of the colon appeared to be completely healed in mice given the combination. Those treated with only parts of the combination or no injection still had actively inflammatory colon lesions, the study showed.
The treatment also reduced the number of colon cancerous tumors that developed by 60% (both animal models and human patients with ulcerative colitis have an increased risk of colon cancer). Furthermore, the injections appeared to target only immune activity against the colon and did not broadly suppress immunity in the body. When the researchers injected ulcerative colitis models into mice that also bore melanoma and colon tumors, these animals responded to immunotherapy for their cancer, which would not have been possible if they were systemically immunosuppressed.
Together, Dr. Wang said, these findings suggest that 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 therapy.
Dr. Wang holds the A. Kenneth Pye Professorship in Cancer Research.
