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Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo

Pizzitola, I., Dos Anjos Afonso, Fernando, Rouault-Pierre, K., Lassailly, F., Tettamanti, S., Spinelli, O., Biondi, A., Biagi, E. and Bonnet, Dominique 2014. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia 28 (8) , pp. 1596-1605. 10.1038/leu.2014.62

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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/progenitor 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Nature Publishing Group:
ISSN: 0887-6924
Last Modified: 21 Feb 2019 15:46
URI: http://orca.cf.ac.uk/id/eprint/74645

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Cited 39 times in Web of Science. View in Web of Science.

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