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Monoclon Antib Immunodiagn Immunother. 2020 Mar 17. doi: 10.1089/mab.2020.0001. [Epub ahead of print]

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

Author information

1
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
2
New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.
3
Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.
4
Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka, Japan.

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.

KEYWORDS:

antibody–drug conjugate; dog podoplanin; monoclonal antibody

PMID:
32182186
DOI:
10.1089/mab.2020.0001

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