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Advances in Hematology
Volume 2012, Article ID 683065, 10 pages
http://dx.doi.org/10.1155/2012/683065
Research Article

In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against Acute Myeloid Leukemia

1INSERM U590/Equipe Cytokines et Cancer, Centre Léon Bérard, 69373 Lyon Cedex 08, France
2Centro Ricerca “M. Tettamanti”, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Via Donizetti 106, 20052 Monza, Italy
3Pediatrics, Cell Therapy Section, The University of Texas MD Anderson Cancer Center, Houston, 77030 TX, USA
4Pediatric Hematology-Oncology, Center for Cell and Gene Therapy, Texas Children's Cancer Center, Baylor College of Medicine, Houston, 77030 TX, USA
5UCB Celltech, 216 Bath Road, Slough, Berkshire SL1 3WE, UK
6Pediatric Hematology-Oncology, Université Claude Bernard Lyon I, 69373 Lyon Cedex 08, France

Received 19 August 2011; Accepted 5 October 2011

Academic Editor: J. F. San Miguel

Copyright © 2012 A. Dutour et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Genetic engineering of T cells with chimeric T-cell receptors (CARs) is an attractive strategy to treat malignancies. It extends the range of antigens for adoptive T-cell immunotherapy, and major mechanisms of tumor escape are bypassed. With this strategy we redirected immune responses towards the CD33 antigen to target acute myeloid leukemia. To improve in vivo T-cell persistence, we modified human Epstein Barr Virus-(EBV-) specific cytotoxic T cells with an anti-CD33.CAR. Genetically modified T cells displayed EBV and HLA-unrestricted CD33 bispecificity in vitro. In addition, though showing a myeloablative activity, they did not irreversibly impair the clonogenic potential of normal CD34+ hematopoietic progenitors. Moreover, after intravenous administration into CD33+ human acute myeloid leukemia-bearing NOD-SCID mice, anti-CD33-EBV-specific T cells reached the tumor sites exerting antitumor activity in vivo. In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone.