Direct cloning of leukemia-reactive T cells from patients treated with donor lymphocyte infusions shows a relative dominance of hematopoiesis-restricted minor histocompatibility antigen HA-1 and HA-2 specific T cells.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVES: One of the few measurable clinical results obtained by the use of somatic cells in onco hematology is the clear-cut effect donor leukocyte infusions (DLI) in patients with chronic myeloid leukemia (CML) who relapse after an allogeneic bone marrow transplantation (BMT). From then on much research has focused on the use of cells to treat different aspects of oncologic diseases from leukemia relapse to development in BMT recipients. METHODS AND INFORMATION SOURCES: In this review we critically and schematically summarize the cell-based therapies which have led to a clinical application and recapitulate the results. RESULTS AND STATE OF THE ART: Although the overall numbers of successfully treated patients is small, therapy has been shown to be safe and effective in a variety of clinical contexts in oncohematology. PERSPECTIVES: Preliminary data will have to be validated in well designed clinical trials with cells generated by reproducible methods and in accreditated structures working according to Good Manufacturing Practices (GMP).
[Show abstract][Hide abstract] ABSTRACT: Dissociation of graft-versus-leukemia (GvL). effects from graft-versus-host disease (GvHD) is the ultimate goal of allogeneic hematopoietic stem cell transplantation (alloHSCT) in the treatment of hematological malignancies. The pivotal role of donor T cells in both anti-leukemic and anti-host reactivity of allogeneic stem cell grafts has been known since the first transplants for fatal leukemia were performed over 25 years ago. Growing understanding of the T cell-mediated GvL response has revealed the importance of host-type antigen-presenting cells and the capacity of adoptively transferred donor T cells in inducing anti-leukemic responses, and has led to a re-evaluation of the relative roles of the pre-transplant conditioning regimen and the allogeneic stem cell graft. Key advances in clinical practice such as reduced-intensity stem cell transplantation and donor lymphocyte infusions are now routinely applied and allow for the induction of potent antileukemic effects, while GvHD can to some extent be controlled. Other strategies to separate T cell-mediated antileukemic effects from GvHD are antigen-specific adoptive T cell-therapy and recipient lymphocyte infusion (RLI) and these are in an experimental stage. Importantly, a role for alloreactive natural killer cells in mediating GvL without GvHD has emerged in patient studies of MHC haplotype-mismatched alloHSCT. Finally, experimental studies indicate that naturally occurring regulatory T cells may differentially affect GvHD and GvL.
Frontiers in Bioscience 02/2007; 12:4568-94. · 4.25 Impact Factor
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