In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD 33 + acute myeloid leukemia

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

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Article number683065
JournalAdvances in Hematology
Volume2012
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Hematology

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