Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Antitumor Effects of Anti-podoplanin Antibody NZ-1 against Malignant Mesothelioma (#80)

Yasuhiko Nishioka 1 , Shinji Abe 2 , Yuki Morita 3 , Mika kato Kaneko 4 , Masaki Hanibuchi 1 , Hisatsugu Goto 1 , Soji Kakiuchi 1 , Yoshinori Aono 1 , Jun Huang 1 , Atsushi Mitsuhashi 1 , Seidai Sato 1 , Kazuo Minakuchi 3 , Yukinari Kato 4
  1. Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
  2. Practice Room for Clinical Pharmacy, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
  3. Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan
  4. Molecular Tumor Marker Research Team, Global COE Program, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, Yamagata, Japan

Podoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). We previously reported the generation of a rat anti-human podoplanin antibody, NZ-1. However, the direct anti-tumor activity against MPM has not been investigated. In the present study, we examined whether anti-podoplanin antibody NZ-1 showed antitumor effects mediated by antibody-dependent cellular cytotoxicity (ADCC). We used human MPM cell lines and tissues. Expression of podoplanin was examined by using flow cytometry and immunohistochemistry. ADCC activity was measured by 51Cr-release assay. In vivo antitumor effects was examined in a xenograft model of human MPM cells in SCID mice. MPM cell lines in 12/15 (80%) expressed podoplanin and MPM tissues also expressed high level of podoplanin. NZ-1 showed high ADCC activity when rat NK cells were used as effector cells. Administration of NZ-1 with rat NK cells significantly suppressed the growth of human MPM cells expressing podoplanin. These results suggest that podoplanin is a promising target for immunotherapy of mesothelioma with anti-podoplanin antibody having ADCC activity.