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Prepublished online as a Blood First Edition Paper on May 22, 2003; DOI 10.1182/blood-2003-01-0095. This Article Full Text (PDF) All Versions of this Article: 2003-01-0095v1 102/6/2004    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 Laport, G. G Articles by June, C. H Search for Related Content PubMed PubMed Citation Articles by Laport, G. G Articles by June, C. H Social Bookmarking                   What's this? Submitted January 14, 2003 Accepted May 9, 2003 Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin's lymphoma following CD34-selected hematopoietic cell transplantation Ginna G Laport, Bruce L Levine, Edward A Stadtmauer, Stephen J Schuster, Selina M Luger, Stephan Grupp, Nancy Bunin, Frank J Strobl, Julio Cotte, Zhaohui Zheng, Brian Gregson, Patricia Rivers, Robert H Vonderheide, David N Liebowitz, David L Porter, and Carl H June* Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia, PA, USA Bone Marrow and Stem Cell Transplant Program, University of Pennsylvania Medical Center, Philadelphia, PA, USA Department of Pediatrics, The Children's Hosptial of Philadelphia, Philadelphia, PA, USA * Corresponding author; email: cjune{at}mail.med.upenn.edu. We explored the feasibility and toxicity of administering escalating doses of anti-CD3/CD28 ex vivo costimulated T cells as a therapeutic adjunct for patients with relapsed, refractory or chemotherapy-resistant, aggressive non-Hodgkin lymphoma (NHL) following high dose chemotherapy and CD34+-selected hematopoietic cell transplantation (HCT). Sixteen patients had infusions on day 14 after HCT of autologous T cells that had been stimulated using beads coated with anti-CD3 and anti-CD28 monoclonal antibodies. At baseline, the subjects had severe quantitative and functional T cell impairments. The culture procedure partially reversed impaired cytokine responsiveness in T cells in vitro and in vivo. Transient dose-dependent infusion toxicities were observed. There was a rapid reconstitution of lymphocytes, however there were persistent defects in CD4 T cells. Most interestingly, 5 patients had a delayed lymphocytosis between day 30 and day 120 after HCT. Maximal clinical responses included 5 patients with a CR, 7 pts with a PR and 4 patients with stable disease. At a median follow-up of 33 months (range=26-60), 5 pts are alive with stable or relapsed disease and 3 pts remain in CR. In conclusion, this Phase I trial demonstrates that adoptive transfers of autologous costimulated T cells 1) is feasible in heavily pretreated patients with advanced NHL, 2) is associated with a rapid recovery of lymphocyte counts, 3) reverses cytokine activation deficits in vitro and 4) is associated with delayed lymphocytosis in a subset of patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. Coughlin, M. D. Fleming, R. G. Carroll, B. R. Pawel, M. D. Hogarty, X. Shan, B. A. Vance, J. N. Cohen, S. Jairaj, E. M. Lord, et al. Immunosurveillance and Survivin-Specific T-Cell Immunity in Children With High-Risk Neuroblastoma J. Clin. 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