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Oncolytic Adenovirus rAd.DCN Inhibits Breast Tumor Growth and Lung Metastasis in an Immune-Competent Orthotopic

Huiqiang Zhao1,2, Hao Wang2, Fanxuan Kong2

  • 11 Department of Cadre Health Care, Navy General Hospital, Beijing, P.R. China.

Human Gene Therapy
|July 24, 2018
PubMed

Insights

Intravenous delivery of decorin-expressing oncolytic adenovirus (rAd.DCN) effectively inhibits breast cancer lung metastasis by modulating immune responses and key signaling pathways.

Area of Science:

  • Oncology
  • Gene Therapy
  • Immunology

Background:

  • Advanced breast cancer frequently metastasizes to distant sites like the lungs and bones.
  • Current therapeutic strategies to prevent metastasis remain limited.
  • Decorin, a natural inhibitor of transforming growth factor-beta (TGF-β), plays a role in suppressing tumor metastasis.

Purpose of the Study:

  • To evaluate the efficacy of an oncolytic adenovirus expressing decorin (rAd.DCN) in preventing breast cancer metastasis.
  • To compare the effects of intratumoral (i.t.) versus intravenous (i.v.) delivery of rAd.DCN.
  • To elucidate the underlying molecular and immunological mechanisms of rAd.DCN's anti-metastatic effects.

Main Methods:

  • Utilized an immune-competent 4T1 breast tumor model in mice.
  • Administered rAd.DCN via both intratumoral and intravenous routes.
  • Assessed tumor growth, spontaneous lung metastasis, transgene expression, and immune cell responses (cytokines, CD8+ T lymphocytes).
  • Analyzed the regulation of key signaling pathways including wnt/β-catenin, VEGF, and Met.

Main Results:

  • Both i.t. and i.v. delivery of rAd.DCN inhibited primary tumor growth and lung metastasis.
  • Intravenous delivery led to higher virus accumulation in lungs and stronger inhibition of lung metastasis compared to i.t. delivery.
  • rAd.DCN downregulated decorin target genes and epithelial-mesenchymal transition markers.
  • Decorin expression modulated Th1/Th2 cytokine balance, enhanced systemic inflammation, and increased CD8+ T lymphocytes.

Conclusions:

  • rAd.DCN effectively inhibits breast cancer growth and lung metastasis through multiple mechanisms.
  • Intravenous delivery of rAd.DCN is a promising strategy for treating breast cancer lung metastasis.
  • The therapeutic effect involves regulating key oncogenic pathways and modulating antitumor immune responses.
Keywords:
breast cancerdecorinlung metastasisoncolytic adenovirusorthotopic xenograft model

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