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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2643-2652. Prepublished online as a Blood First Edition Paper on December 13, 2005; DOI 10.1182/blood-2005-09-3904. This Article Full Text (PDF) Supplemental Figure and Videos All Versions of this Article: 2005-09-3904v1 107/7/2643    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 Serrano, L. M. Articles by Cooper, L. J Search for Related Content PubMed PubMed Citation Articles by Serrano, L. M. Articles by Cooper, L. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 30, 2005 Accepted November 8, 2005 Differentiation of naive cord blood T cells into CD19-specific cytolytic effectors for post-transplant adoptive immunotherapy Lisa Marie Serrano, Timothy Pfeiffer, Simon Olivares, Tontanai Numbenjapon, Jennifer Bennitt, Daniel Kim, David Smith, George McNamara, Zaid Al-Khadimi, Joseph Rosenthal, Stephen J Forman, Michael C Jensen, and Laurence J Cooper* Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Biomedical Informatics, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Cancer Immunotherapeutics & Tumor Immunology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Pediatric Oncology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Cancer Immunotherapeutics & Tumor Immunology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Pediatric Oncology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Pediatric Oncology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA * Corresponding author; email: LCooper{at}coh.org. Disease relapse is a barrier to achieving therapeutic success after unrelated umbilical cord blood transplantation (UCBT) for B-lineage acute lymphoblastic leukemia (B-ALL). While adoptive transfer of donor-derived tumor-specific T cells is a conceptually attractive approach to eliminating residual disease after allogeneic hematopoietic stem-cell transplant, adoptive immunotherapy after UCBT is constrained by the difficulty of generating antigen-specific T cells from functionally naive umbilical cord blood (UCB)-derived T cells. Therefore, to generate T cells that recognize B-ALL, we have developed a chimeric immunoreceptor to redirect the specificity of T cells for CD19, a B-lineage antigen, and expressed this transgene in UCB-derived T cells. An ex vivo process, which is compliant with current good manufacturing practice for T-cell trials, has been developed to genetically modify and numerically expand UCB-derived T cells into CD19-specific effector cells. These are capable of CD19-restricted cytokine production and cytolysis in vitro, as well as mediating regression of CD19+ tumor and being selectively eliminated in vivo. Moreover, time lapse microscopy of the genetically modified T-cell clones revealed an ability to lyse CD19+ tumor cells specifically and repetitively. These data provide the rationale for infusing UCB-derived CD19-specific T cells after UCBT to reduce the incidence of CD19+ B-ALL relapse. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Q. Tang, B. Grzywacz, H. Wang, N. Kataria, Q. Cao, J. E. Wagner, B. R. Blazar, J. S. Miller, and M. R. Verneris Umbilical Cord Blood T Cells Express Multiple Natural Cytotoxicity Receptors after IL-15 Stimulation, but Only NKp30 Is Functional J. Immunol., October 1, 2008; 181(7): 4507 - 4515. [Abstract] [Full Text] [PDF] H. Singh, P. R. Manuri, S. Olivares, N. Dara, M. J. Dawson, H. Huls, P. B. Hackett, D. B. Kohn, E. J. Shpall, R. E. Champlin, et al. Redirecting Specificity of T-Cell Populations For CD19 Using the Sleeping Beauty System Cancer Res., April 15, 2008; 68(8): 2961 - 2971. [Abstract] [Full Text] [PDF] H. Singh, L. M. Serrano, T. Pfeiffer, S. Olivares, G. McNamara, D. D. Smith, Z. Al-Kadhimi, S. J. Forman, S. D. Gillies, M. C. Jensen, et al. Combining Adoptive Cellular and Immunocytokine Therapies to Improve Treatment of B-Lineage Malignancy Cancer Res., March 15, 2007; 67(6): 2872 - 2880. [Abstract] [Full Text] [PDF] E. Biagi, V. Marin, G. M. P. Giordano Attianese, E. Dander, G. D'Amico, and A. Biondi Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies Haematologica, March 1, 2007; 92(3): 381 - 388. [Abstract] [Full Text] [PDF] J. N. Barker Umbilical Cord Blood (UCB) Transplantation: An Alternative to the Use of Unrelated Volunteer Donors? Hematology, January 1, 2007; 2007(1): 55 - 61. [Abstract] [Full Text] [PDF] C. M. Kowolik, M. S. Topp, S. Gonzalez, T. Pfeiffer, S. Olivares, N. Gonzalez, D. D. Smith, S. J. Forman, M. C. Jensen, and L. J.N. Cooper CD28 Costimulation Provided through a CD19-Specific Chimeric Antigen Receptor Enhances In vivo Persistence and Antitumor Efficacy of Adoptively Transferred T Cells. Cancer Res., November 15, 2006; 66(22): 10995 - 11004. [Abstract] [Full Text] [PDF]

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