Pizzitola, I., Anjos-Afonso, Fernando ORCID: https://orcid.org/0000-0003-4392-488X, Rouault-Pierre, K., Lassailly, F., Tettamanti, S., Spinelli, O., Biondi, A., Biagi, E. and Bonnet, D. 2014. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia 28 , pp. 1596-1605. 10.1038/leu.2014.62 |
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 |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences European Cancer Stem Cell Research Institute (ECSCRI) |
Publisher: | Springer Nature |
ISSN: | 0887-6924 |
Date of Acceptance: | 31 January 2014 |
Last Modified: | 22 Jun 2023 10:00 |
URI: | https://orca.cardiff.ac.uk/id/eprint/74645 |
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