Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding

L Yang1, L Wang, X-q Su

  • 1State Key Laboratory of Biotherapy, West China Hospital, School of life Science, Sichuan University, Gaoxin District, Chengdu, Sichuan, PRC.

Cancer Gene Therapy
|July 18, 2009
PubMed

Insights

Liposome-complexed adenoviral vectors delivering endostatin show promise for treating advanced cancers by enhancing gene delivery and reducing immune response. This novel approach effectively targets CAR-negative ovarian cancer cells, inhibiting tumor growth and angiogenesis.

Area of Science:

  • Oncology
  • Gene Therapy
  • Nanomedicine

Background:

  • Adenoviral vectors for cancer gene therapy face limitations due to host immune responses and low coxsackie-adenovirus receptor (CAR) expression.
  • Liposome complexation offers a strategy to overcome these barriers, improving gene delivery and reducing immunogenicity.

Purpose of the Study:

  • To investigate the antitumor effects of PEG-PE cationic liposome-encapsulated recombinant human endostatin adenovirus (Ad-hEndo) in CAR-negative ovarian cancer.
  • To assess the safety, efficacy, and mechanism of action of this novel gene delivery system.

Main Methods:

  • Electron microscopy confirmed efficient encapsulation of adenoviral vectors within PEG-PE cationic liposomes.
  • In vivo studies involved intravenous administration of Ad-hEndo/liposomes in immunocompetent mice and a human ovarian cancer model.
  • Analysis included assessment of transfection efficiency, antibody response, tumor growth, micro-vessel density, and apoptosis.

Main Results:

  • Liposome encapsulation facilitated CAR-independent adenovector transduction and enhanced transfection efficiency.
  • Prolonged systemic administration in mice did not elicit a significant antibody response.
  • Ad-hEndo/liposomes demonstrated well-tolerated systemic administration, marked tumor growth suppression, reduced angiogenesis, and increased tumor cell apoptosis in ovarian cancer models.

Conclusions:

  • PEG-PE cationic liposome-encapsulated Ad-hE (Ad-hE/Lipo) offers a viable intravenous delivery method for gene therapy targeting angiogenesis.
  • This approach shows significant potential for clinical application in treating advanced cancers, particularly ovarian cancer.

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