By exploiting mechanisms that enable cancer cells to evade an immune attack, researchers at UT Southwestern Medical Center have developed a new strategy in animal models that has the potential for treating ulcerative colitis. Their results, reported in Nature Biomedical Engineering, could ultimately provide relief to millions of people around the world suffering from this or other autoimmune diseases.
„We’re borrowing something that cancer uses for evil and turning it into something that’s good,“ said lead author Andrew Wang, MD, professor and vice chair for translational research and commercialization in the Department of Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Wang led the study with first author Kin Man Au, Ph.D., an assistant professor of radiation oncology.
For decades, researchers have known that the immune system can recognize and kill cancer, and thus keep most malignant diseases in check. However, cancer can develop the ability to elude the immune system and produce proteins within their microenvironment that suppress the activity of immune cells and allow tumors to thrive. Conversely, autoimmune diseases arise when the immune system mistakes healthy cells for foreign invaders, triggering unnecessary immune assaults.
Dr. Wang and his colleagues realized they could mimic cancer’s rules and train the immune system to suppress its activity against specific cell types attacked in autoimmune diseases. Previous studies used this approach in animal models for type 1 diabetes and multiple sclerosis.
This latest study focuses on ulcerative colitis, a chronic disease characterized by an autoimmune attack on colon cells. There is no cure for this and other autoimmune diseases, which typically are treated with systemic immunosuppressants that can reduce inappropriate immune activity but have long-term health complications, including increased infection and cancer risks.
The researchers worked with an established mouse model for ulcerative colitis that mimics the severe colon inflammation and damage in human patients. Dr. Wang, Au, and their colleagues injected the animals with a mixture of colon cells and the extracellular matrix that typically surrounds them – a simulation of the tissue usually attacked in ulcerative colitis – along with chemically modified polymer nanofibers that carry a variety of proteins and other tumor-inducing molecules. Cells use these to suppress immune activity.
These injections not only significantly reduced the symptoms of ulcerative colitis such as diarrhea, rectal bleeding, weight loss, and inflammation-related colon shortening, but also tissue analysis showed that this treatment reduced the infiltration of immune cells into the colon lining and their concentration of inflammation molecules. Within seven days of the injection, the researchers found that the colon lining in mice that received the combination appeared to be fully healed. The study found that those treated only with parts of the combination or no injection at all still had actively inflamed colonic lesions.
The treatment also reduced the number of cancerous colon tumors developed by 60% (both animal models and human patients with ulcerative colitis are at increased risk for colon cancer). Moreover, the injections seemed to target only the immune activity against the colon and did not suppress immunity across the body. When the researchers administered injections to mouse models of ulcerative colitis also carrying melanomas and colon tumors, these animals responded to an immunotherapy against their cancer, something not possible with systemic immunosuppression.
Collectively, Dr. Wang said, these results suggest that combination injections could be a feasible new method for treating ulcerative colitis. A similar approach could also be used to treat other autoimmune diseases. He and his colleagues have filed a patent to turn this strategy into a clinical treatment.
Dr. Wang holds the A. Kenneth Pye Professorship in Cancer Research.
UT Southwestern Medical Center