Humanization of fibroblast growth factor 1 single-chain antibody and validation for its antitumorigenic efficacy in breast cancer and glioma cells

J Cell Mol Med. 2018 Jun;22(6):3259-3263. doi: 10.1111/jcmm.13547. Epub 2018 Mar 24.

Abstract

Single-chain variable fragment (scFv) antibodies are the smallest immunoglobulins with high antigen-binding affinity. We have previously reported that fibroblast growth factor 1 played pivotal roles in cancer development and generated a mouse scFv (mscFv1C9) could effectively prohibit cancer cell proliferation in vitro and in vivo. Here, we further humanized this scFv (hscFv1C9) using a structure-guided complementarity determining region grafting strategy. The purified hscFv1C9 maintained similar antigen-binding affinity and specificity as mscFv1C9, and it was capable of inhibiting growth of different tumours in vitro and in vivo. These data strongly suggested that hscFv1C9 has antitumour potentials.

Keywords: antibody humanization; cancer treatment; fibroblast growth factor 1; monoclonal antibody; single-chain variable fragment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblast Growth Factor 1 / antagonists & inhibitors*
  • Fibroblast Growth Factor 1 / chemistry
  • Fibroblast Growth Factor 1 / genetics
  • Fibroblast Growth Factor 1 / immunology
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Heterografts
  • Humans
  • Mice
  • Single-Chain Antibodies / immunology
  • Single-Chain Antibodies / pharmacology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Single-Chain Antibodies
  • Fibroblast Growth Factor 1