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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-07-2142. This Article Full Text (PDF) All Versions of this Article: 2002-07-2142v1 101/2/476    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 Berger, C. Articles by Heimfeld, S. Search for Related Content PubMed PubMed Citation Articles by Berger, C. Articles by Heimfeld, S. Social Bookmarking                   What's this? Submitted July 18, 2002 Accepted August 10, 2002 CD28 costimulation and immunoaffinity-based selection efficiently generate primary gene-modified T cells for adoptive immunotherapy Carolina Berger*, C Anthony Blau, Tim Clackson, Stanley R Riddell, and Shelly Heimfeld Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Division of Hematology, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA ARIAD Gene Therapeutics, Cambridge, MA, USA Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA * Corresponding author; email: cberger{at}fhcrc.org. The introduction of an inducible suicide gene has been proposed as a strategy to exploit the antitumor reactivity of donor T cells after allogeneic hematopoietic stem cell transplantation but permit control of graft-versus-host disease. However, there are several obstacles to this approach that may impair the ability of T cells to function and survive in vivo. These include the requirement for in vitro activation or long-term culture to introduce the transgene and obtain therapeutic cell numbers, the toxicity of drug selection to enrich transduced cells, and the immunogenicity of the transgene-encoded products. Here we have developed a transduction and selection strategy for generating large numbers of polyclonal T cells transduced with a retroviral vector encoding the human low-affinity nerve growth factor receptor (LNGFR) for selection and a Fas-based suicide construct (LV'VFas). Ligation of CD28 in conjunction with a TCR signal permitted efficient transduction, substantially promoted T-cell growth, and contributed to the generation of gene-modified T cells that retained clonal diversity, functional properties, and a homing receptor profile similar to untransduced peripheral blood lymphocytes. Microbeads conjugated directly to antibody specific to LNGFR significantly improved the immunomagnetic selection of LV'VFas-modified T cells and assisted in scaling of the selection procedure to therapeutic cell numbers. Thus, these studies identified a strategy that requires only a brief ex vivo culture and does not utilize drug selection to obtain large numbers of functional gene-modified polyclonal T cells that can be used for adoptive immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Deschamps, P. Mercier-Lethondal, J. M. Certoux, C. Henry, B. Lioure, C. Pagneux, J. Y. Cahn, E. Deconinck, E. Robinet, P. Tiberghien, et al. Deletions within the HSV-tk transgene in long-lasting circulating gene-modified T cells infused with a hematopoietic graft Blood, December 1, 2007; 110(12): 3842 - 3852. [Abstract] [Full Text] [PDF] B. Clemenceau, N. Congy-Jolivet, G. Gallot, R. Vivien, J. 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