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Leukemia. 2014 Aug;28(8):1596-605. doi: 10.1038/leu.2014.62. Epub 2014 Feb 7.

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

Author information

1
1] Department of Pediatrics, Centro di Ricerca 'Matilde Tettamanti', University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy [2] Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
2
Haematopoietic Stem Cell Laboratory, London Research Institute, Cancer Research UK, London, UK.
3
Department of Pediatrics, Centro di Ricerca 'Matilde Tettamanti', University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
4
Department of Haematology, Ospedale Riuniti, Bergamo, Italy.

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.

PMID:
24504024
DOI:
10.1038/leu.2014.62
[Indexed for MEDLINE]

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