One risk associated with allogeneic stem
cell transplants is graft-versus-host-disease (GVHD) during which the donated immune cells fail to
recognize the patient's own tissues and organs. The symptoms of GVHD
vary and can be life-threatening. Common symptoms include rash, nausea
and vomiting, diarrhea, and occasionally jaundice and liver failure.
‘A novel treatment can effectively inhibit the development of graft-versus-host-disease (GVHD) in mice and maintain the infection- and tumor-fighting capabilities of the immune system.’
In order to reduce the risk of GVHD, physicians try to match the
recipient and donor tissue types as close as possible and prophylactic
medicine is given 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 against residual leukemia or lymphoma cells.
new study published as the cover story in Science Translational
, Moffitt Cancer Center researchers show that a novel treatment
can effectively inhibit the development of GVHD in mice and maintain the
infection- and tumor-fighting capabilities of the immune system.
"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," said Betts. "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 Betts.