Identification of anti-CD16a single domain antibodies and their application in bispecific antibodies

Cancer Biol Ther. 2020;21(1):72-80. doi: 10.1080/15384047.2019.1665953. Epub 2019 Sep 29.

Abstract

CD16a (FcγRIIIa) mediates the antibody dependent cellular cytotoxicity (ADCC) and is important for anti-tumor activities of many therapeutic antibodies. Bispecific antibody targeting natural killer (NK) cells has been studied for cancer therapy. In this work, anti-CD16a single-domain antibodies were identified from hCD16a immunized camel. Bispecific antibodies are then constructed by fusing these single domain antibodies with an anti-CEA single domain antibody. These bispecific antibodies can recruite NK cells to kill CEA-positive tumor cells, and inhibit tumor growth in vivo, suggesting that these anti-CD16a single domain antibodies are powerful tools to engaging NK cells for cancer therapy.

Keywords: CD16a; CEA; VHH; bispecific antibody; phage display; single domain antibody.

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / pharmacology*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity*
  • Apoptosis
  • Cell Proliferation
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Peptide Library
  • Receptors, IgG / immunology*
  • Single-Domain Antibodies / immunology
  • Single-Domain Antibodies / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • FCGR3A protein, human
  • Peptide Library
  • Receptors, IgG
  • Single-Domain Antibodies