title: 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.affiliation: INSERM U590/Equipe Cytokines et Cancer, Centre Léon Bérard, 69373 Lyon Cedex 08, France.
authors.forename: A
authors.initials: A
authors.lastname: Dutour
authors.forename: V
authors.initials: V
authors.lastname: Marin
authors.forename: I
authors.initials: I
authors.lastname: Pizzitola
authors.forename: S
authors.initials: S
authors.lastname: Valsesia-Wittmann
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Yvon
authors.forename: H
authors.initials: H
authors.lastname: Finney
authors.forename: A
authors.initials: A
authors.lastname: Lawson
authors.forename: M
authors.initials: M
authors.lastname: Brenner
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: E
authors.initials: E
authors.lastname: Biagi
authors.forename: R
authors.initials: R
authors.lastname: Rousseau