Antibody-Drug Conjugates Using Mouse-Canine Chimeric Anti-Dog Podoplanin Antibody Exerts Antitumor Activity in a Mouse Xenograft Model

Yukinari Kato, Yuji Ito, Tomokazu Ohishi, Manabu Kawada, Takuro Nakamura, Yusuke Sayama, Masato Sano, Teizo Asano, Miyuki Yanaka, Saki Okamoto, Saori Handa, Yu Komatsu, Junko Takei, Mika K. Kaneko

Research output: Contribution to journalArticlepeer-review

Abstract

Antibody-drug conjugates (ADCs), which consist of a monoclonal antibody (mAb), a linker, and a payload, can deliver a drug to cancer tissues. We previously produced an anti-dog podoplanin (dPDPN) mAb, PMab-38, which reacts with dPDPN-expressing canine melanomas and squamous cell carcinomas (SCCs), but not with dPDPN-expressing canine type I alveolar cells or lymphatic endothelial cells, indicating that PMab-38 possesses cancer specificity. In this study, we developed an ADC, P38B-DM1, using the mouse-canine chimeric anti-dPDPN antibody, P38B as the antibody, a peptide linker, and emtansine as the payload using the chemical conjugation by affinity peptide (CCAP) method. We investigated its cytotoxicity against dPDPN-overexpressed Chinese hamster ovary (CHO/dPDPN) cells in vitro and its antitumor activity using a mouse xenograft model of CHO/dPDPN cells. P38B-DM1 showed cytotoxicity to CHO/dPDPN cells in a dose-dependent manner in vitro. Furthermore, P38B-DM1 exhibited higher antitumor activity than P38B in the mouse xenograft model. These results suggest that P38B-DM1, developed using the CCAP method, is useful for antibody therapy against dPDPN-expressing canine SCCs and melanomas.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalMonoclonal antibodies in immunodiagnosis and immunotherapy
Volume39
Issue number2
DOIs
Publication statusPublished - 2020 Apr

Keywords

  • antibody-drug conjugate
  • dog podoplanin
  • monoclonal antibody

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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