Research Group

  • Dr Diana Metes, Principal Investigator
  • Dr Iulia Popescu, Research Associate
  • Ms Yun Hua, Research Technician
  • Ms Louise Smith, Research Nurse
  • Dr Steve Webber, Collaborator
  • Dr Angus Thomson, Collaborator

Location

  • University of Pittsburgh, Pittsburgh, USA

Title

  • Immune Cells for Therapy of Post-transplant Lymphoproliferative Disorders in Pediatric Transplant Patients

Organ transplantation is being increasingly used as a treatment for patients with terminal diseases. While this offers increased expectancy of survival, the long-term results are disappointing. Some of the reasons are related to administration of immunosuppressive drugs to inhibit the reaction of the immune system to the new organ. Unfortunately, these drugs have non-specific effects, inhibiting the immune system and making the patients susceptible to infections and cancer. When a patient, most frequently a child, has received a transplant that by chance contains a certain virus (e.g. Epstein-Barr virus [EBV]) for which the patient does not have immunity, there is a high chance that the immune system of the patient will be unable to control virus multiplication. Post-transplant lympho-proliferative disorders (PTLD) are complications of transplantation, threatening both the survival of the graft and of the patient. No studies are available to explain why this complication occurs only in some patients, nor how to predict who is at high risk. Here we will study dendritic cells natural killer cells and T cells (from blood of patients at risk of complications vs. stable patients) that help the host’s immune system control the viral infection. We will elucidate by in-depth analysis why these cells are comparatively poor stimulators of immune responses in children, and which molecules are specifically not functioning in children with PTLD. In addition, only 70% of the current treatments to eliminate PTLD have been successful. Therefore we will design novel strategies to stimulate and correct defects in body’s immune cells, to become potent at eliminating the EBV-tumors. Our results will aid in providing novel treatments for PTLD and improve transplant outcomes and patient survival.