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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2793-2802. Prepublished online as a Blood First Edition Paper on July 17, 2007; DOI 10.1182/blood-2007-02-072843. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-02-072843v1 110/8/2793    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 Quintarelli, C. Articles by Dotti, G. Search for Related Content PubMed PubMed Citation Articles by Quintarelli, C. Articles by Dotti, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 8, 2007 Accepted July 12, 2007 Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor specific cytotoxic T lymphocytes Concetta Quintarelli, Juan F Vera, Barbara Savoldo, Greta MP Giordano Attianese, Martin Pule, Aaron Foster, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, and Gianpietro Dotti* Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States * Corresponding author; email: gdotti{at}bcm.tmc.edu. The anti-tumor effect of adoptively transferred tumor-specific cytotoxic T lymphocytes (CTLs) is impaired by the limited capacity of these cells to expand within the tumor microenvironment. Administration of IL-2 has been used to overcome this limitation, but the systemic toxicity and the expansion of unwanted cells, including regulatory T cells, limit the clinical value of this strategy. To discover whether transgenic expression of lymphokines by the CTLs themselves might overcome these limitations, we evaluated the effects of transgenic expression of IL-2 and IL-15 in our model of Epstein Barr Virus-specific CTLs (EBV-CTLs). We found that transgenic expression of IL-2 or IL-15 increased the expansion of EBV-CTLs both in vitro and in vivo in a SCID mouse model, and enhanced anti-tumor activity. Although the proliferation of these cytokine genes transduced CTLs remained strictly antigen dependent, clinical application of this approach likely requires the inclusion of a suicide gene to deal with the potential development of T-cell mutants with autonomous growth. We found that the incorporation of an inducible caspase-9 suicide gene allowed efficient elimination of transgenic CTLs after exposure to a chemical inducer of dimerization, thereby increasing the safety and feasibility of the approach. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Warrior, miscreant, suicide: making better killers Mark E. Dudley Blood 2007 110: 2781-2782. [Full Text] [PDF] 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] 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] C. U. Louis, K. Straathof, C. M. Bollard, C. Gerken, M. H. Huls, M. V. Gresik, M.-F. Wu, H. L. Weiss, A. P. Gee, M. K. Brenner, et al. Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients Blood, March 12, 2009; 113(11): 2442 - 2450. [Abstract] [Full Text] [PDF] A. Boni, P. Muranski, L. Cassard, C. Wrzesinski, C. M. Paulos, D. C. Palmer, L. Gattinoni, C. S. Hinrichs, C.-C. Chan, S. A. Rosenberg, et al. Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriers Blood, December 1, 2008; 112(12): 4746 - 4754. [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] C. Quintarelli, G. Dotti, B. De Angelis, V. Hoyos, M. Mims, L. Luciano, H. E. Heslop, C. M. Rooney, F. Pane, and B. Savoldo Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia Blood, September 1, 2008; 112(5): 1876 - 1885. [Abstract] [Full Text] [PDF]

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