TY - JOUR
T1 - Antibody-Drug Conjugates Using Mouse-Canine Chimeric Anti-Dog Podoplanin Antibody Exerts Antitumor Activity in a Mouse Xenograft Model
AU - Kato, Yukinari
AU - Ito, Yuji
AU - Ohishi, Tomokazu
AU - Kawada, Manabu
AU - Nakamura, Takuro
AU - Sayama, Yusuke
AU - Sano, Masato
AU - Asano, Teizo
AU - Yanaka, Miyuki
AU - Okamoto, Saki
AU - Handa, Saori
AU - Komatsu, Yu
AU - Takei, Junko
AU - Kaneko, Mika K.
N1 - Funding Information:
This research was supported in part by Japan Agency for Medical Research and Development (AMED) under Grant Nos: JP19am0401013 (Y.K.), 19am0401002 (Y.I.), JP19am0101078 (Y.K.), and JP19ae0101028 (Y.K.), and by Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Nos: 17K07299, M.K.K; and 19K07705, Y.K.).
Publisher Copyright:
© Yukinari Kato et al. 2020; Published by Mary Ann Liebert, Inc. 2020.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - antibody-drug conjugate
KW - dog podoplanin
KW - monoclonal antibody
UR - http://www.scopus.com/inward/record.url?scp=85083293747&partnerID=8YFLogxK
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U2 - 10.1089/mab.2020.0001
DO - 10.1089/mab.2020.0001
M3 - Article
C2 - 32182186
AN - SCOPUS:85083293747
SN - 2167-9436
VL - 39
SP - 37
EP - 44
JO - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
JF - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
IS - 2
ER -
