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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3890-3897. Prepublished online as a Blood First Edition Paper on August 22, 2006; DOI 10.1182/blood-2006-04-017061. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-04-017061v1 108/12/3890    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 Vera, J. Articles by Dotti, G. Search for Related Content PubMed PubMed Citation Articles by Vera, J. Articles by Dotti, G. Related Collections Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA T lymphocytes redirected against the light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells Juan Vera, Barbara Savoldo, Stephane Vigouroux, Ettore Biagi, Martin Pule, Claudia Rossig, Jessie Wu, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, and Gianpietro Dotti From the Center for Cell and Gene Therapy, Baylor College of Medicine, Methodist Hospital and Texas Children's Hospital, Houston. There has been interest in generating T cells expressing chimeric artificial receptors (CARs) targeting CD19/CD20 antigens to treat B-cell lymphomas. If successful, however, this approach would likely impair humoral immunity because T cells may persist long-term. Most low-grade lymphoma and chronic lymphocytic leukemia (B-CLL) cells express monoclonal immunoglobulins carrying either or light chains. We, therefore, explored whether T lymphocytes could be genetically modified to target the tumor-associated light chain, sparing B lymphocytes expressing the reciprocal light chain, and consequently reduce impairment of humoral immunity. We found that T lymphocytes expressing the anti- light chain CAR showed cytotoxic activity against Ig+ tumor cell lines and B-CLL cells both in vitro and in vivo. We also found that the incorporation of the CD28 endodomain within the CAR enhanced the in vitro and in vivo expansion of transgenic T cells after tumor-associated antigen stimulation. Free Ig+ did not compromise the ability of redirected T lymphocytes to eliminate Ig+ tumors because these free immunoglobulins served to sustain proliferation of CAR-CD28 transgenic T cells. Thus, adoptive transfer of T lymphocytes targeting the appropriate light chain could be a useful immunotherapy approach to treat B-lymphocyte malignancies that clonally express immunoglobulin without entirely compromising humoral immunity. 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] 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] J. Maher and S. Wilkie CAR Mechanics: Driving T Cells into the MUC of Cancer Cancer Res., June 1, 2009; 69(11): 4559 - 4562. [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] K. Dobrenkov, M. Olszewska, Y. Likar, L. Shenker, G. Gunset, S. Cai, N. Pillarsetty, H. Hricak, M. Sadelain, and V. Ponomarev Monitoring the Efficacy of Adoptively Transferred Prostate Cancer-Targeted Human T Lymphocytes with PET and Bioluminescence Imaging J. Nucl. Med., July 1, 2008; 49(7): 1162 - 1170. [Abstract] [Full Text] [PDF] 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] C. Quintarelli, J. F. Vera, B. Savoldo, G. M. P. Giordano Attianese, M. Pule, A. E. Foster, H. E. Heslop, C. M. Rooney, M. K. Brenner, and G. Dotti Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes Blood, October 15, 2007; 110(8): 2793 - 2802. [Abstract] [Full Text] [PDF] B. Savoldo, C. M. Rooney, A. Di Stasi, H. Abken, A. Hombach, A. E. Foster, L. Zhang, H. E. Heslop, M. K. Brenner, and G. Dotti Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30{zeta} artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease Blood, October 1, 2007; 110(7): 2620 - 2630. [Abstract] [Full Text] [PDF] N. Ahmed, M. Ratnayake, B. Savoldo, L. Perlaky, G. Dotti, W. S. Wels, M. B. Bhattacharjee, R. J. Gilbertson, H. D. Shine, H. L. Weiss, et al. Regression of Experimental Medulloblastoma following Transfer of HER2-Specific T Cells Cancer Res., June 15, 2007; 67(12): 5957 - 5964. [Abstract] [Full Text] [PDF]

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