Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity

Monoclon Antib Immunodiagn Immunother. 2017 Feb;36(1):20-24. doi: 10.1089/mab.2016.0045.

Abstract

The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

Keywords: ADCC; CDC; antitumor activity; monoclonal antibody; podoplanin.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity*
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use*
  • CHO Cells
  • Cell Line, Tumor
  • Complement System Proteins / immunology*
  • Cricetulus
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glycopeptides / immunology
  • Humans
  • Lectins, C-Type / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Nude
  • N-Acetylneuraminic Acid / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CLEC2B protein, human
  • Glycopeptides
  • Lectins, C-Type
  • Membrane Glycoproteins
  • PDPN protein, human
  • Complement System Proteins
  • N-Acetylneuraminic Acid