In a new study using mice, researchers show that a novel treatment can effectively inhibit the development of graft-versus-host-disease (GVHD) and maintain the infection- and tumor-fighting capabilities of the immune system. GVHD is the leading cause of non-relapse associated death in patients who receive stem cell transplants.
GVHD can be a side effect of treating patients with certain types of cancer, such as leukemia or lymphoma, using stem cells donated by another person (called an allogeneic transplant). GVHD occurs when the donated cells view the recipient’s body as foreign and attack it. The symptoms of GVHD can range from mild to life threatening.
To reduce the risk of GVHD, physicians try to match the recipient and donor tissue types as closely as possible and administer prophylactic medicine throughout the transplant process. However, patients may still develop GVHD.
The medications used to prevent GVHD are not very selective and suppress the activity of many different immune cell types, good and bad. As a result, GVHD prevention can increase the risk of serious infections and also inhibit the ability of donor immune cells from fighting residual leukemia or lymphoma cells.
A team of Moffitt Cancer Center researchers led by Brian C. Betts, M.D., have been working to develop drugs that can block those components of the immune system that contribute to GVHD without affecting the components of the immune system important for fighting infections and the tumor cells.
“It is known that Aurora kinase A and JAK2 pathway activation contributes to GVHD. However, drugs that inhibit either protein alone do not completely prevent GVHD,” Dr. Betts said. “We hypothesized that co-treatment with drugs that target both Aurora kinase A and JAK2 could prevent GVHD better than either drug alone.”
The researchers discovered that combined inhibition of Aurora kinase A and JAK2 promotes the differentiation of potent regulatory T cells, specialized immune cells that prevent GVHD. Aurora kinase A and JAK2 also significantly reduced GVHD in mice and allowed for the development of anti-cancer immune cells. This was best demonstrated by a drug developed at Moffitt that inhibits both Aurora kinase A and JAK2 simultaneously, eliminating the need to use two different medications.
“This novel prevention strategy warrants further investigation because of its potential to reduce the risk of GVHD and possibly be more effective and selective than commonly used GVHD treatments currently available today,” added Dr. Betts.
The study appears this month in Science Translational Medicine.