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Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants
Loredana Ruggeri,1Marusca Capanni,1Elena Urbani,1Katia Perruccio,1Warren D. Shlomchik,2Antonella Tosti,1Sabrina Posati,1Daniela Rogaia,1Francesco Frassoni,3Franco Aversa,1Massimo F. Martelli,1Andrea Velardi1*
T cells that accompany allogeneic hematopoietic grafts for treating
leukemia enhance engraftment and mediate the graft-versus-leukemiaeffect. Unfortunately, alloreactive T cells also cause
graft-versus-hostdisease (GVHD). T cell depletion prevents GVHD but
increases therisk of graft rejection and leukemic relapse. In human
transplants,we show that donor-versus-recipient natural killer
(NK)-cell alloreactivitycould eliminate leukemia relapse and
graft rejection and protectpatients against GVHD. In mice, the
pretransplant infusion ofalloreactive NK cells obviated the need for
high-intensity conditioningand reduced GVHD. NK cell alloreactivity
may thus provide a powerfultool for enhancing the efficacy and safety
of allogeneic hematopoietictransplantation.
1 Department of Clinical and Experimental
Medicine, Section of Hematology and Clinical Immunology, Perugia
University School of Medicine, Perugia, Italy.
2 Department of Medicine, Sections of Hematology and
Oncology, Yale University School of Medicine, New Haven, CT 06520, USA.
3 Department of Hematology, Ospedale San Martino,
Genoa, Italy.
*
To whom correspondence should be addressed. E-mail:
velardi{at}unipg.it
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|Abstract »|Full Text »|PDF »
Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model.
B. J. Kappel, J. Pinilla-Ibarz, A. A. Kochman, J. M. Eng, V. M. Hubbard, I. Leiner, E. G. Pamer, G. Heller, M. R. M. van den Brink, and D. A. Scheinberg (2006)
Blood
107, 2045-2051
|Abstract »|Full Text »|PDF »
Suicide gene therapy of graft-versus-host disease induced by central memory human T lymphocytes.
A. Bondanza, V. Valtolina, Z. Magnani, M. Ponzoni, K. Fleischhauer, M. Bonyhadi, C. Traversari, F. Sanvito, S. Toma, M. Radrizzani, et al. (2006)
Blood
107, 1828-1836
|Abstract »|Full Text »|PDF »
Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction.
D. Pende, R. Castriconi, P. Romagnani, G. M. Spaggiari, S. Marcenaro, A. Dondero, E. Lazzeri, L. Lasagni, S. Martini, P. Rivera, et al. (2006)
Blood
107, 2030-2036
|Abstract »|Full Text »|PDF »
Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation.
G. M. Spaggiari, A. Capobianco, S. Becchetti, M. C. Mingari, and L. Moretta (2006)
Blood
107, 1484-1490
|Abstract »|Full Text »|PDF »
Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation.
R. F. Rousseau, E. Biagi, A. Dutour, E. S. Yvon, M. P. Brown, T. Lin, Z. Mei, B. Grilley, E. Popek, H. E. Heslop, et al. (2006)
Blood
107, 1332-1341
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CD4+CD25+ T Regulatory Cells Suppress NK Cell-Mediated Immunotherapy of Cancer.
M. J. Smyth, M. W. L. Teng, J. Swann, K. Kyparissoudis, D. I. Godfrey, and Y. Hayakawa (2006)
J. Immunol.
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KIR-incompatible hematopoietic-cell transplantation for poor prognosis infant acute lymphoblastic leukemia.
B. Triplett, R. Handgretinger, C.-H. Pui, and W. Leung (2006)
Blood
107, 1238-1239
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HLA-DPB1 matching status has significant implications for recipients of unrelated donor stem cell transplants.
B. E. Shaw, S. G.E. Marsh, N. P. Mayor, N. H. Russell, and J. A. Madrigal (2006)
Blood
107, 1220-1226
|Abstract »|Full Text »|PDF »
KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation.
S. Cooley, V. McCullar, R. Wangen, T. L. Bergemann, S. Spellman, D. J. Weisdorf, and J. S. Miller (2005)
Blood
106, 4370-4376
|Abstract »|Full Text »|PDF »
Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation.
K. Perruccio, A. Tosti, E. Burchielli, F. Topini, L. Ruggeri, A. Carotti, M. Capanni, E. Urbani, A. Mancusi, F. Aversa, et al. (2005)
Blood
106, 4397-4406
|Abstract »|Full Text »|PDF »
Induction of Early Post-Transplant Graft-versus-Leukemia Effects Using Intentionally Mismatched Donor Lymphocytes and Elimination of Alloantigen-Primed Donor Lymphocytes for Prevention of Graft-versus-Host Disease.
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CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-{beta}-dependent manner.
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Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity.
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Natural-killer cells and dendritic cells: "l'union fait la force".
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Blood
106, 2252-2258
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Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
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Cancer Res.
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|Abstract »|Full Text »|PDF »
Critical role of host {gamma}{delta} T cells in experimental acute graft-versus-host disease.
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Blood
106, 749-755
|Abstract »|Full Text »|PDF »
Successful Use of Haploidentical Stem-Cell Transplantation With KIR Mismatch As Initial Therapy for Poor-Risk Myelodysplastic Syndrome.
M. A. Dawson and A. Spencer (2005)
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|Full Text »|PDF »
