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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2838-2845. Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2007-05-091280. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-091280v1 110/8/2838    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 Bollard, C. M. Articles by Heslop, H. E. Search for Related Content PubMed PubMed Citation Articles by Bollard, C. M. Articles by Heslop, H. E. Related Collections Immunobiology Neoplasia Immunotherapy Clinical Trials and Observations Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer Catherine M. Bollard1,4, Stephen Gottschalk1,3, Ann M. Leen1,2, Heidi Weiss4, Karin C. Straathof1,2, George Carrum1,4, Mariam Khalil1, Meng-fen Wu4, M. Helen Huls1, Chung-Che Chang7, M. Victoria Gresik5, Adrian P. Gee1,2,4, Malcolm K. Brenner1,2,4, Cliona M. Rooney1,6, and Helen E. Heslop1,2,4 1 Center for Cell and Gene Therapy, Departments of 2 Pediatrics, 3 Immunology, 4 Medicine, 5 Pathology, and 6 Virology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX; 7 Department of Pathology, Weill Medical College of Cornell University, The Methodist Hospital Research Institute (TMHRI), The Methodist Hospital, Houston, TX Epstein-Barr virus (EBV)–associated tumors developing in immunocompetent individuals present a challenge to immunotherapy, since they lack expression of immunodominant viral antigens. However, the tumors consistently express viral proteins including LMP2, which are immunologically "weak" but may nonetheless be targets for immune T cells. We previously showed that a majority of cytotoxic T lymphocytes (CTLs) reactivated using EBV-transformed B-lymphoblastoid cells lines (LCLs) contained minor populations of LMP2-specific T cells and homed to tumor sites. However, they did not produce remissions in patients with bulky disease. We have now used gene transfer into antigen-presenting cells (APCs) to augment the expression and immunogenicity of LMP2. These modified APCs increased the frequency of LMP2-specific CTLs by up to 100-fold compared with unmodified LCL-APCs. The LMP2-specific population expanded and persisted in vivo without adverse effects. Nine of 10 patients treated in remission of high-risk disease remain in remission, and 5 of 6 patients with active relapsed disease had a tumor response, which was complete in 4 and sustained for more than 9 months. It is therefore possible to generate immune responses to weak tumor antigens by ex vivo genetic modification of APCs and the CTLs so produced can have substantial antitumor activity. This study is registered at http://www.cancer.gov/clinicaltrials (protocol IDs: BCM-H-9936, NCT00062868 [ClinicalTrials.gov] , NCT00070226 [ClinicalTrials.gov] ). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. S. Hinrichs, Z. A. Borman, L. Cassard, L. Gattinoni, R. Spolski, Z. Yu, L. Sanchez-Perez, P. Muranski, S. J. Kern, C. Logun, et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity PNAS, October 13, 2009; 106(41): 17469 - 17474. [Abstract] [Full Text] [PDF] C. S. Hinrichs, A. Kaiser, C. M. Paulos, L. Cassard, L. Sanchez-Perez, B. Heemskerk, C. Wrzesinski, Z. A. Borman, P. Muranski, and N. P. Restifo Type 17 CD8+ T cells display enhanced antitumor immunity Blood, July 16, 2009; 114(3): 596 - 599. [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. W. Nienhuis Development of gene therapy for blood disorders Blood, May 1, 2008; 111(9): 4431 - 4444. [Abstract] [Full Text] [PDF]

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