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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4583-4589. Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-10-3848. This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2004-10-3848v1 105/12/4583    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 Alajez, N. M. Articles by Finn, O. J. Search for Related Content PubMed PubMed Citation Articles by Alajez, N. M. Articles by Finn, O. J. Related Collections Immunobiology Neoplasia Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Therapeutic potential of a tumor-specific, MHC-unrestricted T-cell receptor expressed on effector cells of the innate and the adaptive immune system through bone marrow transduction and immune reconstitution Nehad M. Alajez, Jan Schmielau, Mark D. Alter, Michael Cascio, and Olivera J. Finn From the Department of Immunology and Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA. T-cell receptor (TCR) with unique major histocompatibility complex (MHC)-unrestricted antigen-binding properties was isolated from a human T-cell clone specific for the tumor antigen MUC1. This TCR binds its epitope on the MUC1 protein without the requirement of processing and presentation. A single-chain V/V/C (scTCR) was fused to a CD3 zeta () chain to allow expression on the surface of cells of the innate (granulocytes, macrophages, natural killer [NK] cells) as well as the adaptive (T and B cells) immune system. To test the ability of the cells of the innate immune system to reject a tumor when provided with a tumor antigen-specific TCR, we reconstituted severe combined immunodeficiency (SCID) mice with bone marrow cells transduced with a retroviral vector encoding this receptor and challenged them with a MUC1-positive human tumor. These mice controlled the growth of the tumor significantly better than the control mice. We performed a similar experiment in immunocompetent mice transgenic for human MUC1. Expression of the TCR on large percentages of cells did not result in infiltration or destruction of tissues expressing MUC1. Reconstituted mice controlled the outgrowth of a MUC1-transfected but not the parental control tumor. scTCR expression appears lifelong, suggesting a successful transduction of the self-renewing stem cells. (Blood. 2005;105:4583-4589) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Wilkie, G. Picco, J. Foster, D. M. Davies, S. Julien, L. Cooper, S. Arif, S. J. Mather, J. Taylor-Papadimitriou, J. M. Burchell, et al. Retargeting of Human T Cells to Tumor-Associated MUC1: The Evolution of a Chimeric Antigen Receptor J. Immunol., April 1, 2008; 180(7): 4901 - 4909. [Abstract] [Full Text] [PDF] Y. Zhao, M. R. Parkhurst, Z. Zheng, C. J. Cohen, J. P. Riley, L. Gattinoni, N. P. Restifo, S. A. Rosenberg, and R. A. Morgan Extrathymic Generation of Tumor-Specific T Cells from Genetically Engineered Human Hematopoietic Stem Cells via Notch Signaling Cancer Res., March 15, 2007; 67(6): 2425 - 2429. [Abstract] [Full Text] [PDF]

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