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Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo

Cancer Gene Therapy volume 9, pages 513–521 (2002)Cite this article

Abstract

A variety of approaches has demonstrated that interfering with tumor-induced angiogenesis may be an effective strategy in cancer therapy. However, it is likely that to be most effective such strategies will require extended suppression of the angiogenic process. Gene therapy offers a possible approach to achieve sustained release of a therapeutically potent transferred gene product. In the present study the angiogenesis inhibitor endostatin was expressed through a recombinant adeno-associated viral (rAAV) vector and shown to be biologically active in vitro and in vivo. Intramuscular injection of rAAV-HuEndo (1×109 i.u.) led to a sustained serum endostatin level of ∼35–40 ng/mL. This endostatin level was sufficient to inhibit tumor cell–induced angiogenesis and to suppress both the initiation and subsequent growth of a human colorectal cancer model.

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Acknowledgements

This work was supported by USPNS Grant CA89655 and a STOP! Children's Cancer Research Grant of the University of Florida. Christian Teschendorf was supported by a fellowship from the Deutsche Krebshilfe, Mildred-Scheel Stiftung.

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Author notes

  1. Wenyin Shi and Christian Teschendorf: Both contributed equally and should be considered first author.

Authors and Affiliations

  1. Department of Pharmacology and Experimental Therapeutics, Shands Cancer Center, University of Florida, Gainesville, 32610, Florida, USA

    Wenyin Shi & Dietmar W Siemann

  2. Gene Therapy Center, Shands Cancer Center, University of Florida, Gainesville, 32610, Florida, USA

    Christian Teschendorf & Nicholas Muzyczka

  3. Department of Radiation Oncology, Shands Cancer Center, University of Florida, Gainesville, 32610, Florida, USA

    Dietmar W Siemann

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  1. Wenyin Shi
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  2. Christian Teschendorf
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Correspondence to Dietmar W Siemann.

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Shi, W., Teschendorf, C., Muzyczka, N. et al. Adeno-associated virus–mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo. Cancer Gene Ther 9, 513–521 (2002). https://doi.org/10.1038/sj.cgt.7700463

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