Children's National Health System researchers, joining other teams, have uncovered new evidence that T-cells, a type of blood cells, can effectively restore antiviral immunity after transplantation for some of the most high-risk viruses following transplant.
In a study published in Science Translational Medicine the researchers determined the feasibility and safety of using naïve-donor-derived T-cells from cord blood for transplant recipients afflicted with cytomegalovirus (CMV), a Herpes virus that can be dormant in the body for years but have potential serious long-term impacts. The naïve T-cells, which are “inexperienced” immune system cells, were trained in the lab to kill virus-infected cells.
The findings open the door for advanced treatment alternatives to address CMV and other viruses, including Epstein-Barr virus (EBV) and adenovirus, in which patients are at high risk after undergoing transplants using cord blood where immunity was not built up, says Patrick Hanley, PhD, Director of GMP for Immunology at the Children’s Research Institute. He is also an assistant professor in the Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, and the Sheikh Zayed Institute for Pediatric Surgical Innovation.
When transplant recipients have a donor who has not been exposed to viruses, they are at great risk because the donor may not have what’s known as “memory” virus-specific T-cells for protection.
To overcome those risks, Hanley’s team, headed by Catherine Bollard, MD, director of Children’s National’s Cell Enhancement and Technologies for Immunotherapy (CETI) Program, was among the first group of scientists to show they can generate virus-specific T-cells even from those cells, which had not built up immunities before, known as “naïve” cells. They could include adult blood donors, as well as cord blood, which is from the umbilical cord after childbirth.
The latest study takes it a step further, by isolating “inexperienced” cells from adult donors who have not had the CMV infection before. They did so by using antibodies bound to magnetic beads and selecting cells that are presented with proteins derived from the virus. In this way, they expanded T-cells against CMV that could be infused into patients.
“Now we are able to expand virus-specific T-cells from inexperienced or CMV negative donors,” Dr. Hanley said, “which we have not been able to do in the past.” Dr. Hanley is director of the good manufacturing practices facility at Children’s National, a highly specialized “clean room” facility where cells are manufactured for patients enrolled on cell therapy clinical trials.
The study also is significant because it shows for the first time that virus-killing T-cells elicited from virus naïve adult and cord blood donors are safe and may prevent infection in high-risk patients afflicted with different viruses, Dr. Bollard said. There are a potential “wide-range of implications” for other viruses, such as Ebola and HIV (the human immunodeficiency virus) that causes AIDS, Dr. Bollard said.
Dr. Hanley conducted the work while completing his training with Dr. Bollard in the Graduate School of Biomedical Sciences at the Baylor College of Medicine. A second study is now open at Children’s National, and two patients have been treated on this protocol.
Dr. Bollard is corresponding author of the study. She had previously been a professor of pediatrics at Baylor. She joins Dr. Hanley as part of a multidisciplinary team conducting follow-up clinical studies working with the Division of Blood and Marrow Transplantation and the Clinical and Translational Science Institute.
Other investigators on the study from Children’s National include Conrad Russell Cruz, MD, Sharon Lam, MD, as well as John Barrett, MD, from the National Heart, Lung, and Blood Institute (NHLBI), and Daniel Douek, MD, from the National Institute of Allergy and Infectious Diseases (NIAH).
Contact: Emily Hartman at 202-476-4500.###