Down-regulation of vascular endothelial growth factor expression by anti-Her2/neu single chain antibodies

Foroogh Nejatollahi1, Mahdi Asgharpour, Mansooreh Jaberipour

  • 1Recombinant Antibody Laboratory, Department of Immunology, Graduate School for Advanced Biomedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Insights

Three novel anti-HER2/neu antibodies effectively reduced vascular endothelial growth factor (VEGF) in HER2/neu-positive breast cancer cells. These findings suggest potential anti-angiogenic therapies for HER2-positive breast cancers.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • HER2/neu overexpression occurs in 25-30% of breast tumors.
  • HER2/neu signaling promotes tumor angiogenesis via vascular endothelial growth factor (VEGF).

Purpose of the Study:

  • To evaluate the anti-angiogenic potential of novel anti-HER2/neu single chain-Fv (scFv) antibodies.
  • To assess the impact of these antibodies on VEGF expression in HER2/neu-positive breast cancer cells.

Main Methods:

  • Panning a human scFv library against HER2/neu epitopes.
  • Treating BT-474 breast cancer cells with anti-HER2/neu scFv antibodies.
  • Quantifying VEGF gene transcript levels using quantitative real-time PCR.
  • Analyzing VEGF protein expression via western blot.

Main Results:

  • All three tested anti-HER2/neu scFv antibodies significantly inhibited VEGF expression.
  • Inhibition of VEGF was observed at both the gene and protein levels.
  • Combined treatment with the scFv antibodies also demonstrated anti-angiogenic effects.

Conclusions:

  • Anti-HER2/neu recombinant antibodies show promise as anti-angiogenic agents.
  • These antibodies could be a valuable therapeutic strategy for HER2-positive breast cancers by targeting angiogenesis.

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