Inhibition of tumor angiogenesis by a single-chain antibody directed against vascular endothelial growth factor

A Vitaliti1, M Wittmer, R Steiner

  • 1Department of Pathology, University Hospital, Zurich, Switzerland.

Cancer Research
|September 2, 2000
PubMed

Insights

Single-chain antibody fragments (scFvs) targeting vascular endothelial growth factor (VEGF) effectively inhibit tumor growth and vascularization. This offers a promising avenue for gene therapy in treating angiogenesis-dependent diseases.

Area of Science:

  • Biotechnology
  • Oncology
  • Molecular Biology

Background:

  • Vascular Endothelial Growth Factor (VEGF) is a key driver of angiogenesis, essential for tumor growth.
  • Monoclonal antibodies (mAbs) targeting VEGF inhibit tumor growth but face challenges in production and administration.
  • Single-chain antibody fragments (scFvs) offer advantages for large-scale production and gene therapy applications.

Purpose of the Study:

  • To develop and characterize anti-VEGF scFvs for potential therapeutic use.
  • To evaluate the efficacy of these scFvs in preclinical models of angiogenesis-dependent diseases.

Main Methods:

  • Generation of anti-VEGF scFvs using a human phage-display library.
  • Assessment of anti-angiogenic activity by blocking chick embryo chorioallantoic membrane vascularization.
  • Evaluation of tumor growth inhibition in nude mouse models with subcutaneous tumors.

Main Results:

  • Successfully derived human anti-VEGF scFvs with potent anti-angiogenic properties.
  • Demonstrated significant inhibition of chick embryo chorioallantoic membrane vascularization.
  • Showed a reduction in subcutaneous tumor growth in nude mice treated with the anti-VEGF scFvs.

Conclusions:

  • Anti-VEGF scFvs are effective inhibitors of angiogenesis and tumor growth.
  • scFvs represent a viable alternative to mAbs for treating angiogenesis-dependent diseases.
  • This research paves the way for gene therapy-based strategies utilizing scFvs for cancer treatment.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...