Endostatin therapy reveals a U-shaped curve for antitumor activity.

Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Cancer Gene Therapy (Impact Factor: 2.95). 07/2006; 13(6):619-27. DOI: 10.1038/sj.cgt.7700938
Source: PubMed

ABSTRACT Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression in the circulation after intramuscular injection in mice. Elevated levels of endostatin remained stable in the circulation for at least 4 months. In vitro assays determined that the protein expressed was biologically active. Antitumor activities of the above construct demonstrated a U-shape curve, where the maximum activity was observed within a certain critical concentration range. These data suggest that an optimum dose range may be required to achieve therapeutic efficacy in large animal models.

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