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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2620-2630. Prepublished online as a Blood First Edition Paper on May 16, 2007; DOI 10.1182/blood-2006-11-059139. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-059139v1 110/7/2620    most recent e-Letter: Submit a Response Alert me when this article is cited Alert me when e-Letters are posted 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 Savoldo, B. Articles by Dotti, G. Search for Related Content PubMed PubMed Citation Articles by Savoldo, B. Articles by Dotti, G. Social Bookmarking                         What's this?  Previous Article  |  Next Article  Submitted November 27, 2006 Accepted May 3, 2007 Epstein barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30 artificial chimeric T-cell receptor for immunotherapy of Hodgkin's disease Barbara Savoldo*, Cliona M Rooney, Antonio Di Stasi, Hinrich Abken, Andreas Hombach, Aaron E Foster, Lan Zhang, Helen E Heslop, Malcolm K Brenner, and Gianpietro Dotti 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 Tumor Genetics, University Hospital Cologne, Cologne, Germany Department of Medicine, 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 * Corresponding author; email: bsavoldo{at}bcm.tmc.edu. Adoptive transfer of Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (EBV-CTLs) has shown that these cells expand and persist in patients with EBV+ Hodgkin's lymphoma (HD), to produce complete tumor responses. Treatment failure, however, occurs if a subpopulation of malignant cells in the tumor lacks or loses expression of EBV-antigens. We have therefore determined whether we could prepare EBV-CTLs that retained the anti-tumor activity conferred by their native receptor whilst expressing a chimeric antigen receptor (CAR) specific for CD30, a molecule highly and consistently expressed on malignant Hodgkin Reed-Sternberg cells. We made a CD30CAR and were able to express it on 26%±11% and 22%±5% of EBV-CTLs generated from healthy donors and HD patients, respectively. These CD30CAR+ CTLs killed both autologous EBV+ cells through their native receptor and EBV-/CD30+ targets through their MHC-unrestricted CAR. A subpopulation of activated T-cells also express CD30, but the CD30CAR+ CTLs did not impair cellular immune responses, likely because normal T-cells express lower levels of the target antigen. In a xenograft model, CD30CAR+ EBV-CTLs could be co-stimulated by EBV-infected cells and produce anti-tumor effects even against EBV-/CD30+ tumors. EBV-CTLs expressing both a native and a chimeric antigen receptor may therefore have added value for treatment of HD. CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this? This article has been cited by other articles: A. A. Chekmasova, T. D. Rao, Y. Nikhamin, K. J. Park, D. A. Levine, D. R. Spriggs, and R. J. Brentjens Successful Eradication of Established Peritoneal Ovarian Tumors in SCID-Beige Mice following Adoptive Transfer of T Cells Genetically Targeted to the MUC16 Antigen Clin. Cancer Res., July 15, 2010; 16(14): 3594 - 3606. [Abstract] [Full Text] [PDF] J. K. Davies, H. Singh, H. 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