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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.
Abstract:
Monoclonal antibody (Ab) directed against the vascular endothelial growth factor, one of the major inducers of angiogenesis, can inhibit tumor growth in mice. Treatment of cancer patients with monoclonal Ab requires large-scale production of the clean Ab and frequent application of the Ab. This might be improved by using single-chain Ab fragments (scFvs), which can be produced in large quantities in bacteria and are attractive for gene therapeutic approaches. Here we describe anti-vascular endothelial growth factor scFvs derived from a human phage-display library able to block the vascularization of the chorioallantoic membrane of chick embryos and reduce the growth of s.c. tumors in nude mice. This work opens the way to develop gene therapy-based strategies using a scFv to treat angiogenesis-dependent diseases.
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.