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Molecular Targets for Therapy

Leukemia targeting ligands isolated from phage display peptide libraries

Leukemia volume 21, pages 411–420 (2007)Cite this article

Abstract

Ligands specifically binding to leukemia cells may be used for drug targeting, resulting in more effective treatment with less side effects. Little is known about receptors specifically expressed on acute myeloid leukemia (AML) cells or ligands thereof. We selected random phage display peptide libraries on Kasumi-1 AML cells. A peptide with the sequence CPLDIDFYC was enriched. Phage displaying this peptide strongly bound to Kasumi-1 and SKNO-1 cells and binding could be inhibited by the cognate peptide. Both, Kasumi-1 and SKNO-1 cells carry the chromosomal translocation t(8;21), leading to aberrant expression of the fusion protein AML1/ETO. CPLDIDFYC also strongly and specifically bound primary AML1/ETO-positive AML blasts as well as U-937 cells with forced AML1/ETO expression, suggesting that the CPLDIDFYC receptor may be upregulated upon AML1/ETO expression. Gene expression profiling comparing a panel of CPLDIDFYC-binding and CPLDIDFYC-nonbinding cell lines identified a set of potential receptors for the CPLDIDFYC peptide. Further analysis suggested that α4β1 integrin (VLA-4) is the CPLDIDFYC receptor. Finally, we showed that the CPLDIDFYC-phage is internalized upon receptor binding, suggesting that the CPLDIDFYC-receptor–ligand interaction may be exploitable for targeting drugs or gene therapy vectors to leukemia cells carrying the suitable receptor.

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Acknowledgements

We thank Drs Florian Otto, Roland Mertelsmann, Christoph Peters, for helpful discussions and critical reading of the manuscript, Drs Renata Pasqualini and Wadih Arap for peptide Stephen Nimer library reagents and helpful comments on this paper and Drs Stephen Nimer, Ursula Kapp, Jens Hasskarl, Ursula Elsässer-Beile, Hanno Glimm, Alexandros Spyridonidis, Uwe Martens for cell lines and Dr George Smith for the fUSE5 plasmid and K91kan bacteria. This work was supported by the Deutsche José Carreras Leukämie-Stiftung (Grants R03/08 to MT and R00/14 to ML).

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  1. S Jäger and A Jahnke: These two authors contributed equally to this work

Authors and Affiliations

  1. Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany

    S Jäger, A Jahnke, T Wilmes, S Adebahr, F-N Vögtle, E deLima-Hahn, D Pfeifer, T Berg, M Lübbert & M Trepel

  2. Institute for Molecular Medicine and Cell Research,, Freiburg, Germany

    M Trepel

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  1. S Jäger
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Jäger, S., Jahnke, A., Wilmes, T. et al. Leukemia targeting ligands isolated from phage display peptide libraries. Leukemia 21, 411–420 (2007). https://doi.org/10.1038/sj.leu.2404548

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