Three-in-one Virus Killer Prevents Common, Often Fatal Infections

A novel combination therapy drastically reduces the infection rate of three viruses -- and risk of death -- in transplant patients with compromised immune systems. The findings, to be reported in the Nov. 1 print edition of Nature Medicine, originate from a study conducted at Baylor College of Medicine, The Methodist Hospital, and Texas Children's Hospital.

The journal has posted the findings online.

The phase 1 trial, funded by the National Heart, Lung, and Blood Institute, one of the National Institutes of Health, tested the first multivirus killer of its kind, called Trivirus-specific cytotoxic T lymphocytes (CTLs), which control infections caused by three commonplace viruses -- cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus. Although benign in people with normal immune systems, the viruses can cause 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.

The other study investigators are Drs. G. Doug Myers, Uluhan Sili, M. Helen Huls, Heidi Weiss, Kathryn S. Leung, George Carrum, Robert A. Krance, Adrian P. Gee, Malcolm K. Brenner, Helen Heslop, and Cliona Rooney, all of BCM, Methodist and Texas Children's.; Dr. Chung-Che Chang, of Cornell University and Methodist; and Dr. Jeffrey J. Molldrem, of The University of Texas M.D. Anderson Cancer Center.

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