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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 Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-059139v1 110/7/2620    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 Savoldo, B. Articles by Dotti, G. Search for Related Content PubMed PubMed Citation Articles by Savoldo, B. Articles by Dotti, G. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Epstein Barr virus–specific cytotoxic T lymphocytes expressing the anti-CD30 artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease Barbara Savoldo1,2, Cliona M. Rooney1,3, Antonio Di Stasi1, Hinrich Abken4, Andreas Hombach4, Aaron E. Foster1, Lan Zhang1, Helen E. Heslop1,2,5, Malcolm K. Brenner1,2,5, and Gianpietro Dotti1,5 1 Center for Cell and Gene Therapy, Departments of2 Pediatrics and 3 Molecular Virology and Microbiology, Baylor College of Medicine, the Methodist Hospital and Texas Children's Hospital, Houston; 4 Tumor Genetics, University of Cologne, Cologne, Germany; 5 Department of Medicine, Baylor College of Medicine, the Methodist Hospital and Texas Children's Hospital, Houston Adoptive transfer of Epstein Barr virus (EBV)–specific cytotoxic T-lymphocytes (EBV-CTLs) has shown that these cells persist in patients with EBV+ Hodgkin 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 antitumor activity conferred by their native receptor while 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 major histocompatibility complex (MHC)–unrestricted CAR. A subpopulation of activated T cells also express CD30, but the CD30CAR+ CTLs did not impair cellular immune responses, probably because normal T cells express lower levels of the target antigen. In a xenograft model, CD30CAR+ EBV-CTLs could be costimulated by EBV-infected cells and produce antitumor 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    Reddit    Technorati    What's this? This article has been cited by other articles: E. Yvon, M. Del Vecchio, B. Savoldo, V. Hoyos, A. Dutour, A. Anichini, G. Dotti, and M. K. Brenner Immunotherapy of Metastatic Melanoma Using Genetically Engineered GD2-Specific T cells Clin. Cancer Res., September 15, 2009; 15(18): 5852 - 5860. [Abstract] [Full Text] [PDF] L. A. Johnson, R. A. Morgan, M. E. Dudley, L. Cassard, J. C. Yang, M. S. Hughes, U. S. Kammula, R. E. Royal, R. M. Sherry, J. R. Wunderlich, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen Blood, July 16, 2009; 114(3): 535 - 546. [Abstract] [Full Text] [PDF] A. Di Stasi, B. De Angelis, C. M. Rooney, L. Zhang, A. Mahendravada, A. E. Foster, H. E. Heslop, M. K. Brenner, G. Dotti, and B. Savoldo T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model Blood, June 18, 2009; 113(25): 6392 - 6402. [Abstract] [Full Text] [PDF] B. A. Rabinovich, Y. Ye, T. Etto, J. Q. Chen, H. I. Levitsky, W. W. Overwijk, L. J. N. Cooper, J. Gelovani, and P. Hwu Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer PNAS, September 23, 2008; 105(38): 14342 - 14346. [Abstract] [Full Text] [PDF] R. F. Ambinder Epstein-Barr Virus and Hodgkin Lymphoma Hematology, January 1, 2007; 2007(1): 204 - 209. [Abstract] [Full Text] [PDF]

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