Marko Radic, PhD, associate professor of Microbiology, Immunology, and Biochemistry in the College of Medicine at the University of Tennessee Health Science Center (UTHSC), has published a paper in Science Translational Medicine that explores a novel treatment option for Systemic lupus erythematosus (SLE) using a targeted immunotherapy approach.
According to the Centers for Disease Control and Prevention, Systemic lupus erythematosus is the most prevalent form of lupus. This autoimmune disease causes the immune system to attack its own tissues, leading to widespread inflammation and tissue damage in the affected organs. It can affect multiple systems including the skin, brain, lungs, kidneys, joints, and blood vessels. Currently, there is no cure for lupus and treatment consists primarily of immunosuppressive drugs that inhibit activity of the immune system.
“There is extensive evidence that self-reactive immunoglobulins, or auto-antibodies, are consistently present in lupus and are responsible for the most severe clinical features, in large part by forming antibody deposits along the surface of blood vessels and various organs in the body,” Dr. Radic said.
Normally, white blood cells called B-cells produce immunoglobulins to fight an infection. Sometimes B-cells produce auto-antibodies that attack one’s own antigens, and this can be a component of various autoimmune diseases such as rheumatoid arthritis or lupus. B-cells can also activate other cells in the immune system called T-cells and can secrete molecules, or cytokines, that worsen inflammatory immune response eliciting disease flares.
“We hypothesized that elimination of cluster of differentiation 19 (CD19)-positive B-cells, the most abundant mature B-cells in the body, would stop the production of autoantibodies and halt the progression of lupus,” he said.
To test their idea, Dr. Radic and his collaborators engineered a new type of T-cell called chimeric antigen receptor (CAR) T- cells, with the support of the Lupus Research Alliance. When tested, these modified CAR T-cells significantly lessened and improved disease symptoms as well as disease progression.
“The most notable effect of our novel treatment method on disease pathogenesis was the increase in lifespan and the lessening of several manifestations of lupus including protein in the urine, skin inflammation, and levels of certain proteins in the blood that are indicators of chronic inflammation,” Dr. Radic said. “This result, which proved effective for over a year, provides clear confirmation that CAR T- cell therapy profoundly stops and even reverses autoimmune disease progression.”
Potential parallels exist between recently-approved CAR T- therapies in cancer and Dr. Radic’s work with lupus as published in his most recent paper. While further research is needed to assess potential risks of this novel therapy option, advances in CAR T-cell technology promise new and more effective treatment options for autoimmune diseases.
“When we awarded Dr. Radic the Novel Research Grant in 2014, using CAR T-cells was just showing promise in cancer, and our scientific advisors recognized the potential of this extremely innovative approach for lupus,” said Kenneth M. Farber, president and CEO of the Lupus Research Alliance. “It has proven transformative for cancer patients, and we hope clinical research can demonstrate safety and effectiveness of CAR T-cells in improving the lives of people with lupus.”