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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokine-Induced Killer Cells / immunology*
  • Humans
  • Interleukin-3 Receptor alpha Subunit / antagonists & inhibitors*
  • Leukemia, Myeloid, Acute / therapy*
  • Mice
  • Mice, SCID
  • Receptors, Antigen / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Sialic Acid Binding Ig-like Lectin 3 / antagonists & inhibitors*
  • T-Lymphocytes / immunology


  • CD33 protein, human
  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Receptors, Antigen
  • Recombinant Fusion Proteins
  • Sialic Acid Binding Ig-like Lectin 3