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

Yukinari Kato, Akiko Kunita, Masashi Fukayama, Shinji Abe, Yasuhiko Nishioka, Hiroaki Uchida, Hideaki Tahara, Shinji Yamada, Miyuki Yanaka, Takuro Nakamura, Noriko Saidoh, Kanae Yoshida, Yuki Fujii, Ryusuke Honma, Michiaki Takagi, Satoshi Ogasawara, Takeshi Murata, Mika K. Kaneko

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20-24
Number of pages5
JournalMonoclonal antibodies in immunodiagnosis and immunotherapy
Volume36
Issue number1
DOIs
Publication statusPublished - 2017 Feb

Keywords

  • ADCC
  • Antitumor activity
  • CDC
  • Monoclonal antibody
  • Podoplanin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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