This is a Shannon award providing partial support for the research projects that fall short of the assigned Institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. DESCRIPTION: (Applicant's Abstract) The applicant's overall aim is to reduce the risk of lethal virus infections that endanger patients after BMT. Particularly deadly is the lymphoproliferative disease caused by EBV. In promising clinical trials at St. Jude's Children's Research Hospital, BMT recipients are receiving EBV-specific memory T cells derived from the marrow donor. Despite favorable preliminary results, three potential problems remain. The problems will be resolved as follows: 1) virus-specific memory T cells may cause graft-versus-host disease. No method has been designed to remove host reactive cells from the donor T cells. The method will be perfected and examined by in vitro testing to ensure that treated cells retain full virus-specific activity. 2) Memory T cells depleted of host reactive cells may lose the capacity to persist and function in vivo. The function of T cells depleted of host reactive cells will be tested in vivo by the use of mouse models. Priming protocols will be designed to optimize virus specific memory T cell activity. 3) Patients may be infected by virulent laboratory stock viruses currently used to expand the virus specific memory T cells in vitro. Protocols will be designed that utilize EBV peptides rather than live virus for T cell stimulations. Individuals from nonminority ethnic groups are already eligible for peptide-based immunotherapeutic programs because their MHC antigens and associated EBV peptides have been studied. To broaden the applicability of peptide-based immunotherapy, the EBV peptides appropriate for T cell triggering in minority/ethnic groups will be defined. BMT is not a routine cancer treatment in many centers, but the risk of serious viral complications remains high.
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