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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1325-1331. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-08-3373. This Article Full Text (PDF) All Versions of this Article: 2005-08-3373v1 107/4/1325    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Porter, D. L Articles by June, C. H Search for Related Content PubMed PubMed Citation Articles by Porter, D. L Articles by June, C. H Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 19, 2005 Accepted October 11, 2005 A phase I trial of donor lymphocyte infusions expanded and activated ex-vivo via CD3/CD28 co-stimulation David L Porter*, Bruce L Levine, Nancy Bunin, Edward A Stadtmauer, Selina M Luger, Steven Goldstein, Alison Loren, Julie Phillips, Sunita Nasta, Alexander Perl, Stephen Schuster, Donald Tsai, Ambika Sohal, Elizabeth Veloso, Stephen G Emerson, and Carl H June Stem Cell Transplant Program and Hematology-Oncology Division, Abramson Cancer Center,, University of Pennsylvania, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA Division of Oncology, Childrens Hospital of Philadelphia, Philadelphia, PA, USA Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA * Corresponding author; email: david.porter{at}uphs.upenn.edu. Donor leukocyte infusions (DLI) induce potent graft-vs-tumor (GVT) effects for relapsed CML after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases. Disease resistance can occur if donor T cells are not appropriately activated in-vivo. Ex-vivo T-cell activation might overcome disease-induced anergy and augment GVT activity. We performed a phase I trial of ex-vivo activated DLI (aDLI) for 18 patients with relapse after SCT. Activated donor T-cells are produced through co-stimulation with anti-CD3 and anti-CD28 coated beads. Patients with aggressive malignancies received induction chemotherapy and all patients received conventional DLI (median 1 .5 x 108 CD3+ cells/kg) followed 12 days later by aDLI. aDLI was dose escalated from 1x106-1x108 CD3+ cells/kg in 5 levels. Seven patients developed acute GVHD (5 grade I-II, 2 grade III) and 4 developed chronic GVHD. Eight patients achieved complete remission including 4/7 ALL, 2/4 AML, 1 CLL and 1/2 NHL. Four complete responders relapsed while 4 remain alive in remission a median 23 months after aDLI. Overall, 10/18 remain alive 11-53 months after aDLI. Adoptive transfer of co-stimulated activated allogeneic T-cells is feasible, does not result in excessive GVHD, and may contribute to durable remissions in diseases where conventional DLI has been disappointing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Klebanoff, Z. Yu, L. N. Hwang, D. C. Palmer, L. Gattinoni, and N. P. Restifo Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination Blood, August 27, 2009; 114(9): 1776 - 1783. [Abstract] [Full Text] [PDF] D. J. Powell Jr and B. L. Levine Adoptive T-cell therapy for malignant disorders Haematologica, October 1, 2008; 93(10): 1452 - 1456. [Full Text] [PDF] B. Vasir, Z. Wu, K. Crawford, J. Rosenblatt, C. Zarwan, A. Bissonnette, D. Kufe, and D. Avigan Fusions of Dendritic Cells with Breast Carcinoma Stimulate the Expansion of Regulatory T Cells while Concomitant Exposure to IL-12, CpG Oligodeoxynucleotides, and Anti-CD3/CD28 Promotes the Expansion of Activated Tumor Reactive Cells J. Immunol., July 1, 2008; 181(1): 808 - 821. [Abstract] [Full Text] [PDF] C. Schmid, M. Labopin, A. Nagler, M. Bornhauser, J. Finke, A. Fassas, L. Volin, G. Gurman, J. Maertens, P. Bordigoni, et al. Donor Lymphocyte Infusion in the Treatment of First Hematological Relapse After Allogeneic Stem-Cell Transplantation in Adults With Acute Myeloid Leukemia: A Retrospective Risk Factors Analysis and Comparison With Other Strategies by the EBMT Acute Leukemia Working Party J. Clin. Oncol., November 1, 2007; 25(31): 4938 - 4945. [Abstract] [Full Text] [PDF] I. G. Schuster, D. H. Busch, E. Eppinger, E. Kremmer, S. Milosevic, C. Hennard, C. Kuttler, J. W. Ellwart, B. Frankenberger, E. Nossner, et al. 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