Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In allogeneic hematopoietic stem cell transplantation (AHSCT) graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect are closely but not invariably linked. Thus, harnessing donor lymphocyte mediated GVL immunity and separating it from GVHD is of particular interest. Based on results obtained in murine models we have explored the CD95-mediated activation-induced cell death (AICD) strategy to selectively deplete alloreactivity in human donor T lymphocytes in vitro. Following stimulation of CD3(+) T cells isolated from HLA-A* 0201-positive donors with HLA or minor histocompatibility antigen mismatched hematopoietic or nonhematopoietic cells in the presence of agonistic anti-CD95 antibody, we achieved efficient and selective allodepletion across major and minor histocompatibility mismatched barriers. Residual alloreactivity was in the range of 10% and 25% using hematopoietic cells and primary keratinocytes as alloantigen-presenting cells, respectively. CD8(+) T cells specific for HLA-A * 0201-associated cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Wilms tumor 1 peptide epitopes were retained at significant numbers within the allodepleted donor lymphocyte subsets. Additionally, CD4(+) FoxP3(+) regulatory T cells persisted after the allodepletion procedure. Our results show that AICD induced by an agonistic anti-CD95 antibody might be useful to generate allodepleted donor lymphocyte products with preserved beneficial immune functions for patients undergoing AHSCT.
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PMID:Depletion of alloreactive donor T lymphocytes by CD95-mediated activation-induced cell death retains antileukemic, antiviral, and immunoregulatory T cell immunity. 1815 66

A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT.
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PMID:Safety and tolerability of allogeneic dendritic cell vaccination with induction of Wilms tumor 1-specific T cells in a pediatric donor and pediatric patient with relapsed leukemia: a case report and review of the literature. 2548 8