The mouse-canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models

Yukinari Kato; Tomokazu Ohishi; Manabu Kawada; Naoya Maekawa; Satoru Konnai; Shunsuke Itai; Shinji Yamada; Mika K Kaneko

doi:10.1016/j.bbrep.2018.11.005

The mouse-canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models

Biochem Biophys Rep. 2018 Nov 24:17:23-26. doi: 10.1016/j.bbrep.2018.11.005. eCollection 2019 Mar.

Authors

Yukinari Kato^{1

2}, Tomokazu Ohishi³, Manabu Kawada³, Naoya Maekawa⁴, Satoru Konnai^{4

5}, Shunsuke Itai¹, Shinji Yamada¹, Mika K Kaneko¹

Affiliations

¹ Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
² New Industry Creation Hatchery Center, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
³ Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.
⁴ Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
⁵ Laboratory of Infectious Diseases, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.

Abstract

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.

Keywords: ADCC, antibody-dependent cellular cytotoxicity; CDC, complement-dependent cytotoxicity; CHO, Chinese hamster ovary; CLEC-2, C-type lectin-like receptor 2; Dog podoplanin; Monoclonal antibody; Mouse-canine chimeric antibody; PBS, phosphate-buffered saline; PDPN, podoplanin; SCC, squamous cell carcinomas; dPDPN; dPDPN, dog podoplanin; mAb, monoclonal antibody.