Viral infections present deadly threats to patients who have received donor blood, marrow, and cord stem cells transplants and are immune deficient while their transplants begin to work. When drugs fail, T-cells specially engineered to target the viruses could help, but generating those when needed presents a major barrier.
In a new study, researchers led by those at Baylor College of Medicine (BCM) found that previously banked third party T-cells that specifically targeted three viruses that threaten recipients of such stem cell transplants offer a potent remedy for patients for whom antiviral drugs are not working.
In their study, the BCM researchers generated a bank of 32 cell lines specific for three viruses - Epstein-Barr, cytomegalovirus, and adenovirus. Each was characterized to identify which viruses it could "see" or recognize so the investigators could identify the most suitable line for each patient. They used cells from 18 of these lines to treat 50 patients from 8 centers across the country that had undergone a stem cell transplant and were suffering from a severe viral infection that had not responded to conventional treatment. Commonly, patients who undergo these stem cell transplants are immune suppressed after the procedure and before the transplanted cells repopulate their immune systems.
Six weeks after the cell infusion, 74 percent of those receiving the treatment had overcome the infection, either partially or completely and only 4 patients later had had a recurrence of the virus or progression of their diseases. This treatment was safe, with only two subjects developing new graft versus host disease in which the grafted T-cells attack the patients' normal cells, but this was mild in both cases and resolved rapidly. The numbers of virus-specific T-cells in their circulation increased after the infusion of the banked cells.
"What’s remarkable about these patients is that they had failed treatment with conventional antiviral therapies and subsequently responded to the T-cells," said Dr. Ann M. Leen (pictured right), assistant professor of pediatrics - hematology/oncology at BCM and a member of the Center for Cell and Gene Therapy at BCM, Texas Children's Hospital and The Methodist Hospital. "Many transplant centers do not have facilities to manufacture T-cell lines to treat viral infections. However, our bank of lines, which can be shipped all over the country, let us provide this new treatment more broadly that was previously possible."
"The standard way of making these cells takes 3 to 4 months," said Dr. Helen Heslop (pictured left), professor of medicine - hematology/oncology at BCM, director of the Stem Cell Transplant program at The Methodist Hospital, and also a member of the Center for Cell and Gene Therapy. "Moreover, we cannot make donor cells for a patient when the donor has never been exposed to the virus."
This method using the banked cells already shortens the wait time and a new method that Leen is developing could shorten the time to prepare the cells to no more than 10 days, said Heslop. She is also exploring the possibility of using the treatment in others patients who have an immune deficiency that could make them prone to life-threatening infections from these viruses.
Illustration: Baylor College of Medicine.
Baylor College of Medicine News Release (05/14/13)
Health Canal (05/14/13)
Abstract (Blood; (04/22/13))