|
|
Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2002-11-3516.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses
Persis J. Amrolia,
Giada Muccioli-Casadei,
Eric Yvon,
Helen Huls,
Uluhan Sili,
Eric D. Wieder,
Catherine Bollard,
Jaroslav Michalek,
Victor Ghetie,
Helen E. Heslop,
Jeffrey J. Molldrem,
Cliona M. Rooney,
John Schlinder,
Ellen Vitetta, and
Malcolm K. Brenner
From the Department of Bone Marrow Transplantation, Great Ormond St Childrens Hospital, London, United Kingdom; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; and Department of Bone Marrow Transplantation, MD Anderson Cancer Center, Houston, TX.
Poor immune reconstitution after haploidentical stem cell transplantation results in a high mortality from viral infections and relapse. One approach to overcome this problem is to selectively deplete the graft of alloreactive cells using an immunotoxin directed against the activation marker CD25. However, the degree of depletion of alloreactive cells is variable following stimulation with recipient peripheral blood mononuclear cells (PBMCs), and this can result in graft versus host disease (GVHD). We have refined this approach using recipient Epstein-Barr virus (EBV)–transformed lymphoblastoid cell lines (LCLs) as stimulators to activate donor alloreactive T cells. Our studies demonstrate that allodepletion with an anti-CD25 immunotoxin following stimulation with HLA-mismatched host LCLs more consistently depleted in vitro alloreactivity than stimulation with host PBMCs, as assessed in primary mixed lymphocyte reactions (MLRs). Allodepletion using this approach specifically abrogates cytotoxic T-cell responses against host LCLs. In interferon- (IFN-) enzyme-linked immunospot (ELISPOT) assays, antiviral responses to adenovirus and cytomegalovirus (CMV) were preserved following allodepletion. Likewise, using HLA-A2–pp65 tetramers, we have shown that the frequency of CMV-specific T cells is unaffected by allodepletion. Moreover, the donor anti-EBV response is partially retained by recognition of EBV antigens through the nonshared haplotype. Finally, we studied whether allodepletion affects the response to candidate tumor antigens in myeloid malignancies. Using HLA-A2–PR1 tetramer analysis, we found that the frequency of T cells recognizing the PR1 epitope of proteinase 3 was not significantly different in allodepleted and unmanipulated PBMCs from patients with chronic myeloid leukemia (CML) undergoing transplantation. Based on these data, we have embarked on a phase 1 clinical trial of addback of allo-LCL–depleted donor T cells in the haplo-identical setting.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Mielke, R. Nunes, K. Rezvani, V. S. Fellowes, A. Venne, S. R. Solomon, Y. Fan, E. Gostick, D. A. Price, C. Scotto, et al.
A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique
Blood,
April 15, 2008;
111(8):
4392 - 4402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mielke, K. Rezvani, B. N. Savani, R. Nunes, A. S. M. Yong, J. Schindler, R. Kurlander, V. Ghetie, E. J. Read, S. R. Solomon, et al.
Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease
Blood,
September 1, 2007;
110(5):
1689 - 1697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. C. Wehler, M. Nonn, B. Brandt, C. M. Britten, M. Grone, M. Todorova, I. Link, S. A. Khan, R. G. Meyer, C. Huber, et al.
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines
Blood,
January 1, 2007;
109(1):
365 - 373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Amrolia, G. Muccioli-Casadei, H. Huls, S. Adams, A. Durett, A. Gee, E. Yvon, H. Weiss, M. Cobbold, H. B. Gaspar, et al.
Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation
Blood,
September 15, 2006;
108(6):
1797 - 1808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Landais, A. Morice, H. M. Long, T. A. Haigh, B. Charreau, M. Bonneville, G. S. Taylor, and E. Houssaint
EBV-Specific CD4+ T Cell Clones Exhibit Vigorous Allogeneic Responses
J. Immunol.,
August 1, 2006;
177(3):
1427 - 1433.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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
Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model
Blood,
March 1, 2006;
107(5):
2045 - 2051.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Grunebaum, E. Mazzolari, F. Porta, D. Dallera, A. Atkinson, B. Reid, L. D. Notarangelo, and C. M. Roifman
Bone Marrow Transplantation for Severe Combined Immune Deficiency
JAMA,
February 1, 2006;
295(5):
508 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. N. Cooper, Z. Al-Kadhimi, L. M. Serrano, T. Pfeiffer, S. Olivares, A. Castro, W.-C. Chang, S. Gonzalez, D. Smith, S. J. Forman, et al.
Enhanced antilymphoma efficacy of CD19-redirected influenza MP1-specific CTLs by cotransfer of T cells modified to present influenza MP1
Blood,
February 15, 2005;
105(4):
1622 - 1631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Watson, G. Y. Zhang, M. Sartor, and S. I. Alexander
"Pruning" of Alloreactive CD4+ T Cells Using 5- (and 6-)Carboxyfluorescein Diacetate Succinimidyl Ester Prolongs Skin Allograft Survival
J. Immunol.,
December 1, 2004;
173(11):
6574 - 6582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. R. Martins, L. S. St. John, R. E. Champlin, E. D. Wieder, J. McMannis, J. J. Molldrem, and K. V. Komanduri
Functional assessment and specific depletion of alloreactive human T cells using flow cytometry
Blood,
December 1, 2004;
104(12):
3429 - 3436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Foster, M. Marangolo, M. M. Sartor, S. I. Alexander, M. Hu, K. F. Bradstock, and D. J. Gottlieb
Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion
Blood,
October 15, 2004;
104(8):
2403 - 2409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Stanzani, S. L. R. Martins, R. M. Saliba, L. S. St. John, S. Bryan, D. Couriel, J. McMannis, R. E. Champlin, J. J. Molldrem, and K. V. Komanduri
CD25 expression on donor CD4+ or CD8+ T cells is associated with an increased risk for graft-versus-host disease after HLA-identical stem cell transplantation in humans
Blood,
February 1, 2004;
103(3):
1140 - 1146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Godfrey, M. R. Krampf, P. A. Taylor, and B. R. Blazar
Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation
Blood,
February 1, 2004;
103(3):
1158 - 1165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Heslop, F. K. Stevenson, and J. J. Molldrem
Immunotherapy of Hematologic Malignancy
Hematology,
January 1, 2003;
2003(1):
331 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
