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In VitroandIn VivoAntitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL againstCD33+Acute Myeloid Leukemia
Author(s) -
Aurélie Dutour,
Virna Marin,
Irene Pizzitola,
Sandrine ValsesiaWittmann,
Dean A. Lee,
Eric Yvon,
Helene M. Finney,
Alastair D. G. Lawson,
Malcolm K. Brenner,
Andrea Biondi,
E. Biagi,
Raphaël F. Rousseau
Publication year - 2012
Publication title -
advances in hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.371
H-Index - 31
eISSN - 1687-9112
pISSN - 1687-9104
DOI - 10.1155/2012/683065
Subject(s) - cd33 , chimeric antigen receptor , cytotoxic t cell , cancer research , immunotherapy , immunology , medicine , myeloid leukemia , t cell , ctl* , cd34 , antigen , myeloid , in vivo , leukemia , immune system , stem cell , in vitro , biology , cd8 , microbiology and biotechnology , biochemistry
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.

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