As significant numbers of acute myeloid leukemia (AML) patients are still refractory to conventional therapies or experience relapse, immunotherapy using T-cells expressing chimeric antigen receptors (CARs) might represent a valid treatment option. AML cells frequently overexpress the myeloid antigens CD33 and CD123, for which specific CARs can be generated. However, CD33 is also expressed on normal hematopoietic stem/progenitors cells (HSPCs), and its targeting could potentially impair normal hematopoiesis. In contrast, CD123 is widely expressed by AML, while low expression is detected on HSPCs, making it a much more attractive target. In this study we describe the in vivo efficacy and safety of using cytokine-induced-killer (CIK) cells genetically modified to express anti-CD33 or anti-CD123 CAR to target AML. We show that both these modified T-cells are very efficient in reducing leukemia burden in vivo, but only the anti-CD123 CAR has limited killing on normal HSPCs, thus making it a very attractive immunotherapeutic tool for AML treatment.Leukemia accepted article preview online, 7 February 2014; doi:10.1038/leu.2014.62.

Pizzitola, I., Anjos Afonso, F., Rouault Pierre, K., Lassailly, F., Tettamanti, S., Spinelli, O., et al. (2014). Chimeric Antigen Receptors against CD33/CD123 antigens efficiently target primary Acute Myeloid Leukemia cells in vivo. LEUKEMIA, 28(8), 1596-1605 [10.1038/leu.2014.62].

Chimeric Antigen Receptors against CD33/CD123 antigens efficiently target primary Acute Myeloid Leukemia cells in vivo

PIZZITOLA, IRENE;BIONDI, ANDREA;BIAGI, ETTORE;
2014

Abstract

As significant numbers of acute myeloid leukemia (AML) patients are still refractory to conventional therapies or experience relapse, immunotherapy using T-cells expressing chimeric antigen receptors (CARs) might represent a valid treatment option. AML cells frequently overexpress the myeloid antigens CD33 and CD123, for which specific CARs can be generated. However, CD33 is also expressed on normal hematopoietic stem/progenitors cells (HSPCs), and its targeting could potentially impair normal hematopoiesis. In contrast, CD123 is widely expressed by AML, while low expression is detected on HSPCs, making it a much more attractive target. In this study we describe the in vivo efficacy and safety of using cytokine-induced-killer (CIK) cells genetically modified to express anti-CD33 or anti-CD123 CAR to target AML. We show that both these modified T-cells are very efficient in reducing leukemia burden in vivo, but only the anti-CD123 CAR has limited killing on normal HSPCs, thus making it a very attractive immunotherapeutic tool for AML treatment.Leukemia accepted article preview online, 7 February 2014; doi:10.1038/leu.2014.62.
Articolo in rivista - Articolo scientifico
AML, CD123, CD33, chimeric antigen receptor
English
2014
28
8
1596
1605
none
Pizzitola, I., Anjos Afonso, F., Rouault Pierre, K., Lassailly, F., Tettamanti, S., Spinelli, O., et al. (2014). Chimeric Antigen Receptors against CD33/CD123 antigens efficiently target primary Acute Myeloid Leukemia cells in vivo. LEUKEMIA, 28(8), 1596-1605 [10.1038/leu.2014.62].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/50264
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