Through cancer immunotherapy research efforts, Andrew Wang, M.D., FAIMBE, FAAAS, Professor of Radiation Oncology and Vice Chair, Translational Research & Commercialization, and his research team are finding novel ways to treat previously incurable autoimmune diseases.
Autoimmune diseases are conditions in which your immune system is overactive, causing it to attack and damage your body’s own tissues. There are more than 100 types of autoimmune diseases, and they affect more than 50 million individuals in the United States alone. Consequently, there is an enormous economic toll, too, especially since autoimmune diseases are essentially incurable and continuously require treatment, such as administration of steroids or other medications. In their research on cancer immunotherapy, Dr. Wang and his research group recognized two lessons: high levels of immune checkpoint molecules can induce immune tolerance despite many tumor mutations; and immune checkpoint blockade treatment can lead to side effects and diseases that mirror autoimmune disease, such as colitis and diabetes. Based on these observations, they hypothesized that engineering more checkpoint ligands onto normal cells can potentially induce tolerance of normal cells and reverse autoimmunity. They developed a new platform technology called Checkpoint Ligand Engineering for Autoimmune Restoration (CLEAR) to explore potential treatments and cures for autoimmune diseases. This highly innovative approach translates principles adopted from tumor immunology to autoimmune disease treatment and shows great promise thus far.
Specifically, this technique leverages existing human biology and immune checkpoint pathways. In this research, CLEAR can modify normal cells in the body to express high levels of immune checkpoint molecules, and these engineered cells can then be administered to patients. Injecting these cells into patients can trigger systemic tolerance and ultimately reverse autoimmune reactions, thereby functioning in a therapeutic capacity.
“Cancer is a terrible disease, and we have learned a lot from cancer research and treatment,” Dr. Wang says. “We are applying these lessons learned beyond cancer treatment and trying to use the strategies that cancer cells use to induce immune tolerance for good treatment of autoimmune diseases. If successful, this will improve the lives of many patients.”
In this work, which was recently published in Nature Biomedical Engineering, Dr. Wang and his group used preclinical mouse models to show that using CLEAR is effective and reversed colitis/inflammatory bowel disease.
“We engineered mini-colons and equipped them with extra immune suppressive molecules,” he says. “We showed that these engineered mini-colons can reverse acute and chronic colitis. In addition, the treatment is highly specific. We showed that mice with both cancer and colitis can be treated by these engineered mini-colons, and the mini-colon treatment did not affect the cancer immunotherapy treatment.”
To translate this technology to clinical practice, Dr. Wang is working hard to build a new biotechnology company. With investment, they will be able to develop the necessary steps to manufacture engineered cells and initiate clinical trials. These studies are currently supported by Department startup funds and are awaiting additional funding.