Isolation of anti-VEGF monoclonal antibodies with neutralizing effects from an Astragalus-induced immune antibody library

Yu Ching Lee, Hsien Te Huang, Chao Di Chang, Chin Tien Chen, Tsai Yu Lin, Tz Wen Yang, Fu Ling Chang, Mei Kuang Lu, Chun Tang Chiou, Wang Chuan Chen, Shiow Lin Pan, Keng Chang Tsai

Research output: Contribution to journalArticlepeer-review

Abstract

The Astragalus membranaceus polysaccharides (APS) can improve immunity and enhance treatment reactions. This study analyzed the effects of effective antivascular endothelial growth factor (anti-VEGF) antibody production in mice treated with APS. After APS treatment, the serum of mice produced the antibody reactions that can cross-validate VEGF. The isolated single-chain fragment variable (scFv) antibodies could neutralize VEGF and inhibit in vivo tumor growth. Of the scFvs, scFv 4E can significantly compete the interaction of bevacizumab with VEGF. In cell experiments, scFv 4E effectively inhibited human umbilical vein endothelial cells induced by VEGF in vitro. In a matrix gel-assisted angiogenesis model, scFv 4E significantly inhibited angiogenesis reactions. In addition, in a xenograft model established in the colorectal cancer cell strain HCT116, scFv 4E treatment inhibited tumor growth by up to 52.7%. Finally, molecule docking was performed to simulate the complex interactions of scFv 4E and VEGF, the main driving forces of which involve the hydrophobic interactions and hydrogen bonds of Tyr108 and Tyr 109 of the complementarity-determining region H3 loop with VEGF. The results help in establishing antibody library with high diversity for selecting antibodies with specificity. In addition, this study indirectly expounded the correlations of APS enhancing immunity regulation in vivo.

Original languageEnglish
Article number107007
JournalInternational Immunopharmacology
Volume88
DOIs
Publication statusPublished - Nov 1 2020

Keywords

  • Angiogenesis
  • Astragalus membranaceus polysaccharides
  • Molecule docking
  • Single-chain fragment variable antibodies
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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