In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against CD 33 + Acute Myeloid Leukemia

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 C...

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Bibliographic Details
Published in:Advances in hematology 2012, Vol.2012, p.1-10
Main Authors: Dutour, A., Marin, V., Pizzitola, I., Valsesia-Wittmann, S., Lee, D., Yvon, E., Finney, H., Lawson, A., Brenner, M., Biondi, A., Biagi, E., Rousseau, R.
Format: Article
Language:English
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Summary: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.
ISSN:1687-9104
1687-9112
DOI:10.1155/2012/683065