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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6392-6402. Prepublished online as a Blood First Edition Paper on April 17, 2009; DOI 10.1182/blood-2009-03-209650. This Article Full Text (PDF) All Versions of this Article: blood-2009-03-209650v1 113/25/6392    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 Di Stasi, A. Articles by Savoldo, B. Search for Related Content PubMed PubMed Citation Articles by Di Stasi, A. Articles by Savoldo, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 9, 2009 Accepted April 6, 2009 T lymphocytes co-expressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and anti-tumor activity in a Hodgkin's tumor model Antonio Di Stasi, Biagio De Angelis, Cliona M. Rooney, Lan Zhang, Aruna Mahendravada, Aaron E. Foster, Helen E. Heslop, Malcolm K. Brenner, Gianpietro Dotti, and Barbara Savoldo* Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, United States Department of Molecular Virology and Microbiology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, United States Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, United States Department of Medicine, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, United States Department of Immunology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, United States * Corresponding author; email: bsavoldo{at}bcm.tmc.edu. For the adoptive transfer of tumor-directed T lymphocytes to prove effective, there will likely need to be a match between the chemokines the tumor produces and the chemokine receptors the effector T cells express. The Reed-Stemberg cells of Hodgkin lymphoma (HL) predominantly produce thymus- and activation-regulated chemokine/CC chemokine ligand 17 (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), which preferentially attract type 2 T helper (Th2) cells and regulatory T cells (Tregs) that express the TARC/MDC-specific chemokine receptor CCR4, thus generating an immunosuppressed tumor environment. By contrast, effector CD8+ T cells lack CCR4, are nonresponsive to these chemokines and are rarely detected at the tumor site. We now show that forced expression of CCR4 by effector T cells enhances their migration to HL cells. Furthermore, T lymphocytes expressing both CCR4 and a chimeric antigen receptor directed to the HL associated antigen CD30 sustain their cytotoxic function and cytokine secretion in vitro, and produce enhanced tumor control when infused intravenously in mice engrafted with human HL. We conclude that this approach may be of value in patients affected by HL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. De Angelis, G. Dotti, C. Quintarelli, L. E. Huye, L. Zhang, M. Zhang, F. Pane, H. E. Heslop, M. K. Brenner, C. M. Rooney, et al. Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506) Blood, November 26, 2009; 114(23): 4784 - 4791. [Abstract] [Full Text] [PDF]

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