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Human blood late outgrowth endothelial cells for gene therapy of cancer: determinants of efficacy

Gene Therapy volume 14, pages 344–356 (2007)Cite this article

Abstract

Human adult blood late outgrowth endothelial cells (BOECs) are potential yet untested cellular vehicles to target tumor-cytotoxic effectors to tumors. We show that, following intravenous injection into irradiated mice, BOECs home to Lewis lung carcinoma (LLC) lung metastases, but less so to liver or kidney metastases. BOECs targeted most but not all of the lung metastases, to a different degree. While most of the homed BOECs took up an extravascular position, some integrated into tumor vessels. Sequestration into normal tissue was low. Placental growth factor mediated both migration and invasion of BOECs into LLC spheroid masses in vitro, as did VEGF. When armed with a suicide gene, BOECs exerted a bystander effect on LLC cells in vitro and in vivo. Surprisingly, i.v. administration of armed BOECs into mice bearing multi-organ LLC metastases did not prolong survival. In addition to homing efficacy other parameters impacted upon the efficacy of BOECs. These include the ultimate susceptibility of BOECs to suicide gene-induced cell death, their paracrine proliferative effect on LLC cells and their low proliferation rate compared to LLC cells. Addressing these determinants may make BOECs a useful addition to the arsenal of tumor-targeting moieties.

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Acknowledgements

We thank H Ribbert from the Department of Nuclear Medicine for help in preparing and detecting 111In-DTP-Ac-LDL-loaded BOECs, M Shibuya for the LLC and LLC-PLGF cell lines, P Vajkoczy for SF126 cells, W Wick for LNT-229 cells and for introducing us to stereotactic manipulations, S Zhou for providing human fibroblasts, S Miebach for introduction to spheroid assays and I Gastrock-Balitsch, U Kirchner and H Knauss for excellent technical help. Supported by a grant from the Wilhelm Sander-Stiftung (to CB).

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  1. J Wei and G Jarmy: These authors contributed equally to this work

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  1. University Children's Hospital, Ulm, Germany

    J Wei, G Jarmy, J Genuneit, K-M Debatin & C Beltinger

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Wei, J., Jarmy, G., Genuneit, J. et al. Human blood late outgrowth endothelial cells for gene therapy of cancer: determinants of efficacy. Gene Ther 14, 344–356 (2007). https://doi.org/10.1038/sj.gt.3302860

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