ChLpMab-23: Cancer-Specific Human-Mouse Chimeric Anti-Podoplanin Antibody Exhibits Antitumor Activity via Antibody-Dependent Cellular Cytotoxicity

Mika K. Kaneko, Takuro Nakamura, Akiko Kunita, Masashi Fukayama, Shinji Abe, Yasuhiko Nishioka, Shinji Yamada, Miyuki Yanaka, Noriko Saidoh, Kanae Yoshida, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Podoplanin is expressed in many cancers, including oral cancers and brain tumors. The interaction between podoplanin and its receptor C-type lectin-like receptor 2 (CLEC-2) has been reported to be involved in cancer metastasis and tumor malignancy. We previously established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23 (IgG1, kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab. However, we have not shown the usefulness of LpMab-23 for antibody therapy against podoplanin-expressing cancers. In this study, we first determined the minimum epitope of LpMab-23 and revealed that Gly54-Leu64 peptide, especially Gly54, Thr55, Ser56, Glu57, Asp58, Arg59, Tyr60, and Leu64 of podoplanin, is a critical epitope of LpMab-23. We further produced human-mouse chimeric LpMab-23 (chLpMab-23) and investigated whether chLpMab-23 exerts antibody-dependent cellular cytotoxicity (ADCC) and antitumor activity. In flow cytometry, chLpMab-23 showed high sensitivity against a podoplanin-expressing glioblastoma cell line, LN319, and an oral cancer cell line, HSC-2. chLpMab-23 also showed ADCC activity against podoplanin-expressing CHO cells (CHO/podoplanin). In xenograft models with HSC-2 and CHO/podoplanin, chLpMab-23 exerts antitumor activity using human natural killer cells, indicating that chLpMab-23 could be useful for antibody therapy against podoplanin-expressing cancers.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalMonoclonal antibodies in immunodiagnosis and immunotherapy
Volume36
Issue number3
DOIs
Publication statusPublished - 2017 Jun

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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