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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3087-3093. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-09-3737. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-09-3737v1 105/8/3087    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Friedmann-Morvinski, D. Articles by Eshhar, Z. Search for Related Content PubMed PubMed Citation Articles by Friedmann-Morvinski, D. Articles by Eshhar, Z. Related Collections Immunobiology Neoplasia Signal Transduction Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Redirected primary T cells harboring a chimeric receptor require costimulation for their antigen-specific activation Dinorah Friedmann-Morvinski, Alain Bendavid, Tova Waks, Daniel Schindler, and Zelig Eshhar From the Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. Chimeric receptor (CR)–redirected lymphocytes (T bodies) have great potential in the eradication of tumor cells. To extend this approach to target cells that do not express surface ligands to costimulatory receptors (eg, cancer cells), we have generated an antibody-based tripartite chimeric receptor (TPCR) that contains scFv linked to the costimulatory molecule, CD28 without its ligand-binding domain, and to the cytoplasmic moiety of the FcR subunit. In this study, we tested the ability of 2,4,6-trinitrophenyl (TNP)–specific TPCR to drive primary, naïve T cells derived from CR-transgenic (Tg) mice to undergo full activation. As a control, we used Tg mice expressing a similar transgene but lacking the signaling region of CD28 (Tg-TPCRCD28). Only T cells from the TPCR-Tg and not the CD28-truncated TPCR-Tg mice could undergo activation following stimulation on hapten-modified target cells not expressing B7. Moreover, when stimulated with TNP protein displayed on plastic, the TPCR-Tg T cells expressing the entire TPCR gene became fully activated for proliferation, interleukin 2 production, protection from apoptosis, and killing of TNP-modified target cells. Finally, TPCR-Tg mice manifested a delayed-type hypersensitivity response following skin challenge in the absence of priming. Taken together, our results suggest that the TPCR is the receptor configuration of choice for clinical applications using primary T or stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Ahmed, M. Ratnayake, B. Savoldo, L. Perlaky, G. Dotti, W. S. Wels, M. B. Bhattacharjee, R. J. Gilbertson, H. D. Shine, H. L. Weiss, et al. Regression of Experimental Medulloblastoma following Transfer of HER2-Specific T Cells Cancer Res., June 15, 2007; 67(12): 5957 - 5964. [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] 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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