TY - JOUR
T1 - The mouse–canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models
AU - Kato, Yukinari
AU - Ohishi, Tomokazu
AU - Kawada, Manabu
AU - Maekawa, Naoya
AU - Konnai, Satoru
AU - Itai, Shunsuke
AU - Yamada, Shinji
AU - Kaneko, Mika K.
N1 - Funding Information:
This research was supported in part by AMED under Grant nos. JP18am0101078 (Y.K.), JP18am0301010 (Y.K.), and JP18ae0101028 (Y.K.), and by JSPS KAKENHI Grant nos. 17K07299 (M.K.K.) and 16K10748 (Y.K.).
Publisher Copyright:
© 2018 The Authors
PY - 2019/3
Y1 - 2019/3
N2 - Podoplanin (PDPN) is a type I transmembrane heavily glycosylated sialoglycoprotein that is expressed in normal tissues such as pulmonary type I alveolar cells, renal podocytes, and lymphatic endothelial cells. PDPN overexpression in cancerous tissue is associated with hematogenous metastasis through interactions with the C-type lectin-like receptor 2 (CLEC-2). Previously, we have reported the development of a mouse monoclonal antibody (mAb), PMab-38 (IgG1, kappa) against dog PDPN (dPDPN). PMab-38 was found to strongly react with canine squamous cell carcinomas (SCCs) and melanomas; however, it showed no reaction with lymphatic endothelial cells. Recently, we have developed and produced the mouse–canine mAb of subclass B, P38B that showed antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against Chinese hamster ovary (CHO)/dPDPN cells. In the present study, we investigated the antitumor activity using mouse xenograft model. To induce ADCC activity by P38B, canine mononuclear cells were injected surrounding the tumors in a xenograft model. It was demonstrated that P38B exerted antitumor activity against the mouse xenograft model using CHO/dPDPN. These results suggest that P38B is useful for antibody therapy against dPDPN-expressing canine SCCs and melanomas.
AB - Podoplanin (PDPN) is a type I transmembrane heavily glycosylated sialoglycoprotein that is expressed in normal tissues such as pulmonary type I alveolar cells, renal podocytes, and lymphatic endothelial cells. PDPN overexpression in cancerous tissue is associated with hematogenous metastasis through interactions with the C-type lectin-like receptor 2 (CLEC-2). Previously, we have reported the development of a mouse monoclonal antibody (mAb), PMab-38 (IgG1, kappa) against dog PDPN (dPDPN). PMab-38 was found to strongly react with canine squamous cell carcinomas (SCCs) and melanomas; however, it showed no reaction with lymphatic endothelial cells. Recently, we have developed and produced the mouse–canine mAb of subclass B, P38B that showed antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against Chinese hamster ovary (CHO)/dPDPN cells. In the present study, we investigated the antitumor activity using mouse xenograft model. To induce ADCC activity by P38B, canine mononuclear cells were injected surrounding the tumors in a xenograft model. It was demonstrated that P38B exerted antitumor activity against the mouse xenograft model using CHO/dPDPN. These results suggest that P38B is useful for antibody therapy against dPDPN-expressing canine SCCs and melanomas.
KW - Dog podoplanin
KW - Monoclonal antibody
KW - Mouse-canine chimeric antibody
KW - dPDPN
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U2 - 10.1016/j.bbrep.2018.11.005
DO - 10.1016/j.bbrep.2018.11.005
M3 - Article
AN - SCOPUS:85057094019
SN - 2405-5808
VL - 17
SP - 23
EP - 26
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
ER -
