A potent therapy to combat fatal viral infections

A study conducted at Baylor College of Medicine, The Methodist Hospital, and Texas Children's Hospital has zeroed in on a recent combination therapy, that holds promise for reducing the infection rate of three viruses, while cutting the lurking danger of death in transplant patients whose immune systems are not up the mark.

The stage1 of the trial sponsored by the National Heart, Lung, and Blood Institute, one of the National Institutes of Health, examined the first multivirus killer,called Trivirus-specific cytotoxic T lymphocytes (CTLs), which direct infections caused by three routine viruses – cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus. Although it is mild in people with normal immune systems, the viruses can trigger life-threatening illnesses in transplant patients and others with compromised immune systems.

The CTLs proved effective and safe in all 11 bone marrow transplant patients, who recovered completely within two to four weeks of being treated without any side effects or toxicity. Preexisting therapies for adenovirus have had little success – there is an 80 percent chance of death following the development of adenovirus.

"Not only were patients prevented from getting these infections after transplant, but those patients who had infections responded to the T-cell therapy and did not require any other treatment," said senior author Dr. Catherine Bollard, assistant professor of pediatrics, immunology, and medicine at BCM and a researcher at the Center for Cell and Gene Therapy at BCM, Methodist and Texas Children's. "To make dramatic recoveries like these was really quite something."

The research team drew cells from bone marrow donors and "trained" T-cells to target the three viruses before injecting them into transplant recipients.

"Drugs only control the virus. They don't cure the underlying problem," said Bollard. "Whereas by introducing these specialized T-cells, we are fixing the underlying problem. Using your own immune system is preferable to chemical agents, which can have toxic side effects."

Although the CTLs must undergo further testing, the early results suggest the combination therapy to be more, cost-effective, and safe than traditional therapies and more practical than cell-based therapies that target EBV and CMV separately, both of which are carried in roughly 80 percent of all people. Adenoviruses are common viruses carried in all populations.

"There is no safe and effective therapy for patients with adenovirus infections at the moment, so if you get an infection after a transplant it becomes very problematic," said first author Dr. Ann Leen, BCM instructor of pediatrics at the Center for Cell and Gene Therapy. "So we trained certain T-cells to target this virus."

Bollard envisions one day extending the application of CTLs to other people with compromised immune systems, such as cancer patients undergoing chemotherapy. The therapy could also potentially be used in babies, who are more susceptible to adenovirus infections than other age groups.

Source-Eurekalert
SAV