This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. CMV reactivation and disease is a significant complication of allogeneic hemopoietic stem cell transplant. In a normal individual cytotoxic T lymphocytes specific for CMV are protective and the risk post transplant correlates with deficiency of a CMV specific immune response in the first 4-6 months post transplant. Adoptive transfer of CMV specific CTLs is a potential approach to reconstituting CMV immunity in these patients and reducing the risk of CMV disease. In a proof of principle study, CMV prophylaxis with adoptively transferred, donor-derived CMV-specific CTL was first explored by Walter et al.1 This group expanded and infused CMV-specific CD8+ clones in a dose-escalation study in allogeneic matched sibling SCT recipients. There were no adverse events and functional CMV-specific CD8+ T-cell responses were detected in all patients following infusion.1 However, because of the requirement for donor fibroblasts as antigen presenting cells, patients receiving transplants from unrelated donors were excluded from this approach. In this study we plan to evaluate a clinically more feasible approach to generate CMV-specific CD4 and CD8+ T cells using dendritic cells transduced with an adenoviral vector encoding the immunodominant CMV antigen pp65 as the antigen presenting cell.2 We hypothesize that we can successfully generate CMVpp65 specific cytotoxic T-cells and adoptively transfer them as CMV prophylaxis to patients at risk for CMV reactivation after allogeneic stem cell transplant. II.
SPECIFIC AIMS 1) To determine the safety, toxicity and maximum tolerated dose (MTD) of one intravenous injection of donor-derived CMV-specific cytotoxic T lymphocytes (CTLs) given as CMV prophylaxis to patients at risk for CMV reactivation after allogeneic stem cell transplant. 2) To evaluate efficacy of recovery of virus-specific immunity after CTL infusion and its correlation with protection from viral reactivation/disease.
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