The UVARXTS system being used in the photopheresis research is currently for investigational use only, pemding FDA approval. Photo Credit : Courtesy Therakos, a Johnson & Johnson Company
ILLUMINATING REJECTION
USC researchers light up the immune system to help heart transplant patients.
by Eva EmersonCapping more than a decade of work, USC associate professor of cardiothoracic surgery Mark L. Barr, M.D., says that a new kind of therapy helps prevent rejection of heart transplants.
The therapy, called photopheresis, combines ultra-violet light and a light-activated drug to suppress certain key immune cells.
Combing photopheresis with standard therapy can reduce the number of serious organ rejections, without increasing side effects, Barr reported in a recent issue of the New England Journal of Medicine.
"It is a much more targeted therapy than what is currently used. Instead of suppressing the entire immune system, photopheresis allows us to suppress primarily those immune cells responsible for rejecting a donated organ," says Barr, who led an international trial of the therapy. "I expect that, in the future, photopheresis will be used for both prevention and treatment of rejection in patients who receive virtually any kind of solid organ transplant."
In the study, a total of 60 heart transplant patients were randomly assigned to receive either photopheresis with standard therapy or standard therapy alone. Patients treated with photopheresis were more than twice as likely to have no episodes of rejection than were patients in the control group. What's more, those receiving standard therapy alone were more than twice as likely to have multiple rejections.
Although transplant medicine has advanced considerably in recent years, some problems remain. Despite the use of powerful drugs to dampen the immune system, many patients experience life-threatening bouts of rejection. In addition, the intense immunosuppression necessary to battle rejection often leaves patients vulnerable to opportunistic infections from viruses like cytomegalovirus (CMV).
The beauty of photopheresis, notes Barr, is it appears to only destroy the cells responsible for attacking the donor organ, leaving the rest of the immune system robust enough to fight off viruses and bacterial infections.
"Patients in the photopheresis group had lower levels of CMV in the bloodstream. That supports the idea that the procedure helps the patient's own immune system to clear the virus," he says.
Photopheresis involves removing blood from patients and then collecting the white cells including T-lymphocytes, or T-cells. T-cells play a key role in mounting a defense against foreign molecules-including a transplanted heart.
The treatment involves mixing the T-cells with a drug called methoxsalen. Exposing the mix to a UV-A light box-similar to something that might be found in a tanning salon-activates the drug, which binds to the T-cells in an irreversible fashion. Patients are then re-injected with their own altered T-cells. Like a vaccine, the inactivated T-cells alert the immune system to destroy any similar T-cells still in the blood.
Photopheresis "changes the way the body views its own cells, so that the immune system will recognize-and eliminate-the very cells that are attacking the transplanted organ," Barr says.
"We see this study as proof of principle, that photopheresis works to change the complicated immune response of transplant patients," says Barr, who has helped move the therapy from an idea to a viable, and sometimes life-saving, therapy.
The study's implications go beyond heart transplant recipients, Barr says. "This therapy may have a dramatic impact on the treatment of potentially lethal rejection in other solid organ transplants, including lung, small bowel and kidney. It has also been applied in bone marrow transplantation to treat or prevent Graft vs. Host Disease," Barr says.
Outside of the present study, he and other researchers have successfully used photopheresis in transplant patients who have been in the midst of near-fatal rejection episodes.
"Some of our patients have clearly been saved by this therapy," he says.
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