AAV-mediated persistent bevacizumab therapy suppresses tumor growth of ovarian cancer. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line, Tumor
  • Female
  • Genetic Vectors
  • Humans
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Xenograft Model Antitumor Assays

MeSH Major

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Carcinoma
  • Cell Proliferation
  • Dependovirus
  • Genetic Therapy
  • Ovarian Neoplasms
  • Tumor Burden

abstract

  • Anti-angiogenesis therapies such as bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), have been used against ovarian cancer, but transient and low peritoneal drug levels are likely a factor in treatment failure. We hypothesized that a single administration of adeno-associated virus (AAV)-mediated intraperitoneal expression of bevacizumab would direct persistent expression and suppress growth and metastasis of ovarian cancer. AAVrh.10BevMab, a rhesus serotype 10 adeno-associated viral vector coding for bevacizumab, was evaluated for the capacity of a single intraperitoneal administration to persistently suppress peritoneal tumor growth in an intraperitoneal model of ovarian carcinomatosis with human ovarian cancer cells in nude immunodeficient mice. The data demonstrates that AAVrh10.BevMab mediates persistent and high levels of bevacizumab in the peritoneal cavity following a single intraperitoneal administration in mice. In AAVrh10.BevMab treated A2780 human ovarian cancer-bearing mice, tumor growth was significantly suppressed (p<0.05) and the area of blood vessels in the tumor was decreased (p<0.04). Survival of mice with A2780 xenografts or SK-OV3 xenografts was greatly prolonged in the presence of AAVrh10.BevMab (p<0.001). Administration of AAVrh10.BevMab 4days after A2780-luciferase cell implantation reduced tumor growth (p<0.01) and increased mouse survival (p<0.0001). Combination of AAVrh10.BevMab with cytotoxic reagents paclitaxel or topotecan proved to be more effective in increasing survival than treatment with cytotoxic reagent alone. A single administration of AAVrh10.BevMab provides sustained and high local expression of bevacizumab in the peritoneal cavity, and significantly suppresses peritoneal carcinomatosis and increases survival in an ovarian cancer murine model. Copyright © 2014 Elsevier Inc. All rights reserved.

publication date

  • November 2014

has subject area

  • Angiogenesis Inhibitors
  • Animals
  • Antibodies, Monoclonal, Humanized
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation
  • Dependovirus
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.ygyno.2014.07.105

PubMed ID

  • 25108232

Additional Document Info

start page

  • 325

end page

  • 332

volume

  • 135

number

  • 2