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

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.

• Authors: A Dutour, V Marin, I Pizzitola, S Valsesia-Wittmann, D Lee, E Yvon, H Finney, A Lawson, M Brenner, A Biondi, E Biagi, R Rousseau
• Journal: Advances in hematology (Adv Hematol) Vol. 2012 Pg. 683065 ( 2012) ISSN: 1687-9112 [Electronic] United States
• PMID: 22272203 (Publication Type: Journal Article)