Dataset Information

Safety and feasibility of virus-specific T cells derived from umbilical cord blood in cord blood transplant recipients.

ABSTRACT: Adoptive transfer of virus-specific T cells (VSTs) has been shown to be safe and effective in stem cell transplant recipients. However, the lack of virus-experienced T cells in donor cord blood (CB) has prevented the development of ex vivo expanded donor-derived VSTs for recipients of this stem cell source. Here we evaluated the feasibility and safety of ex vivo expansion of CB T cells from the 20% fraction of the CB unit in pediatric patients receiving a single CB transplant (CBT). In 2 clinical trials conducted at 2 separate sites, we manufactured CB-derived multivirus-specific T cells (CB-VSTs) targeting Epstein-Barr virus (EBV), adenovirus, and cytomegalovirus (CMV) for 18 (86%) of 21 patients demonstrating feasibility. Manufacturing for 2 CB-VSTs failed to meet lot release because of insufficient cell recovery, and there was 1 sterility breach during separation of the frozen 20% fraction. Delayed engraftment was not observed in patients who received the remaining 80% fraction for the primary CBT. There was no grade 3 to 4 acute graft-versus-host disease (GVHD) associated with the infusion of CB-VSTs. None of the 7 patients who received CB-VSTs as prophylaxis developed end-organ disease from CMV, EBV, or adenovirus. In 7 patients receiving CB-VSTs for viral reactivation or infection, only 1 patient developed end-organ viral disease, which was in an immune privileged site (CMV retinitis) and occurred after steroid therapy for GVHD. Finally, we demonstrated the long-term persistence of adoptively transferred CB-VSTs using T-cell receptor-V? clonotype tracking, suggesting that CB-VSTs are a feasible addition to antiviral pharmacotherapy.

SUBMITTER: Abraham AA

PROVIDER: S-EPMC6650740 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and feasibility of virus-specific T cells derived from umbilical cord blood in cord blood transplant recipients.

Abraham Allistair A AA John Tami D TD Keller Michael D MD Cruz C Russell N CRN Salem Baheyeldin B Roesch Lauren L Liu Hao H Hoq Fahmida F Grilley Bambi J BJ Gee Adrian P AP Dave Hema H Jacobsohn David A DA Krance Robert A RA Shpall Elizabeth J EJ Martinez Caridad A CA Hanley Patrick J PJ Bollard Catherine M CM

Blood advances 20190701 14

Adoptive transfer of virus-specific T cells (VSTs) has been shown to be safe and effective in stem cell transplant recipients. However, the lack of virus-experienced T cells in donor cord blood (CB) has prevented the development of ex vivo expanded donor-derived VSTs for recipients of this stem cell source. Here we evaluated the feasibility and safety of ex vivo expansion of CB T cells from the 20% fraction of the CB unit in pediatric patients receiving a single CB transplant (CBT). In 2 clinica ...[more]

PMID: 31292125

Similar Datasets

Project description:INTRODUCTION:Preterm brain injury continues to be an important complication of preterm birth, especially in extremely premature infants. Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for their neuroprotective and neuroreparative properties in preclinical and clinical studies. There remains a paucity of information on the feasibility and safety of autologous UCBC transplantation in extremely premature infants. METHODS AND ANALYSIS:A single centre safety and feasibility study in preterm babies born before 28 weeks gestation. Cord blood will be collected after birth and if sufficient blood is obtained, UCB mononuclear cells will be harvested from the cord blood, characterised and stored. After excluding infants who have already suffered severe preterm brain injury, based on cranial ultrasounds in first week of life, preterm infants will be infused with autologous UCBCs via the intravenous route at a dose of 25-50?million UCBCs/kg body weight of live cells, with the cell number being the maximum available up to 50?million cells/kg. A minimum of 20 infants will be administered autologous UCBCs. Primary outcomes will include feasibility and safety. Feasibility will be determined by access to sufficient cord blood at collection and UCBCs following processing. Safety will be determined by lack of adverse events directly related to autologous UCBC administration in the first few days after cell administration. Secondary outcomes studied will include neonatal and neurodevelopmental morbidities till 2 years of life. Additional outcomes will include cell characteristics of all collected cord blood, and cytokine responses to cell administration in transplanted infants till 36 weeks' corrected age. ETHICS AND DISSEMINATION:Monash Health Human Research Ethics Committee approved this study in December 2019. Recruitment is to commence in July 2020 and is expected to take around 12 months. The findings of this study will be disseminated via peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER:ACTRN12619001637134.

Dataset Information

Safety and feasibility of virus-specific T cells derived from umbilical cord blood in cord blood transplant recipients.

Publications

Safety and feasibility of virus-specific T cells derived from umbilical cord blood in cord blood transplant recipients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets