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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1622-1631. Prepublished online as a Blood First Edition Paper on October 26, 2004; DOI 10.1182/blood-2004-03-1208. This Article Full Text (PDF) All Versions of this Article: 2004-03-1208v1 105/4/1622    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 Cooper, L. J Articles by Jensen, M. C Search for Related Content PubMed PubMed Citation Articles by Cooper, L. J Articles by Jensen, M. C Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 2, 2004 Accepted October 13, 2004 Enhanced anti-lymphoma efficacy of CD19 redirected influenza MP1-specific CTL's by co-transfer of T-cells modified to present influenza MP1 Laurence J Cooper*, Zaid Al-Kadhimi, Lisa M Serrano, Timothy Pfeiffer, Simon Olivares, Adrian Castro, Wen-Chung Chang, Sergio Gonzalez, David Smith, Stephen J Forman, and Michael C Jensen Division of Pediatric Hematology-Oncology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Bioinformatics, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA Division of Pediatric Hematology-Oncology, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA; Division of Molecular Medicine, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA * Corresponding author; email: lcooper{at}coh.org. To enhance the in vivo anti-tumor activity of adoptively transferred CD19-specific chimeric antigen receptor (CAR) redirected cytotoxic T lymphocytes (CTL's), we studied the effect of restimulating CAR+ CTL's through their endogenous virus-specific T-cell antigen receptor (TcR) by the co-transfer of engineered T-cell antigen-presenting cells (T-APC's). Using influenza A matrix protein 1 (MP1) as a model antigen, we show that ex vivo-expanded CD4+ and CD8+ T-APC's expressing a hygromycin phosphotransferase-MP1 fusion protein (HyMP1), process and present MP1 to autologous HLA-restricted MP1-specific CD4+ and CD8+ CTL-precursors. The MP1-specific CTL's are amenable to subsequent genetic modification to express a CD19-specific CAR, designated CD19R, and acquire HLA-unrestricted reactivity towards CD19+ leukemia and lymphoma tumor targets, while maintaining HLA-restricted MP1 specificity. The re-stimulation of MP1xCD19 dual-specific CTL's in vivo by the adoptive transfer of irradiated HyMP1+ T-APC's resulted in enhanced anti-lymphoma potency of bi-specific effector cells as measured by elimination of the biophotonic signal of established firefly luciferase-expressing Burkitt lymphoma xenografts in NOD/scid animals, in comparison to control groups restimulated by Hy+MP1neg T-APC's. Engineered T-APC's are a novel and versatile antigen-delivery system for generating antigen-specific T cells in vitro and enhancing the in vivo effector functioning of CAR-redirected anti-tumor effector cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] H. Singh, P. R. Manuri, S. Olivares, N. Dara, M. J. Dawson, H. Huls, P. B. Hackett, D. B. Kohn, E. J. Shpall, R. E. Champlin, et al. Redirecting Specificity of T-Cell Populations For CD19 Using the Sleeping Beauty System Cancer Res., April 15, 2008; 68(8): 2961 - 2971. [Abstract] [Full Text] [PDF] C. M. Kowolik, M. S. Topp, S. Gonzalez, T. Pfeiffer, S. Olivares, N. Gonzalez, D. D. Smith, S. J. Forman, M. C. Jensen, and L. J.N. Cooper CD28 Costimulation Provided through a CD19-Specific Chimeric Antigen Receptor Enhances In vivo Persistence and Antitumor Efficacy of Adoptively Transferred T Cells. Cancer Res., November 15, 2006; 66(22): 10995 - 11004. [Abstract] [Full Text] [PDF]

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