@article{011c9e8ee6d647ce98324a92daaddbe9,
title = "Therapeutic efficacy evaluation of radioimmunotherapy with 90Y-labeled anti-podoplanin antibody NZ-12 for mesothelioma",
abstract = "Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is highly expressed in malignant mesothelioma. The rat-human chimeric antibody NZ-12 has high affinity for human podoplanin and antibody-dependent cellular cytotoxicity and is applicable for radioimmunotherapy (RIT) to enhance the antitumor effect. In the present study, we evaluated the in vivo and in vitro properties of radiolabeled NZ-12 and the antitumor effect of RIT with 90Y-labeled NZ-12 in an NCI-H226 (H226) malignant mesothelioma xenograft mouse model. 111In-labeled NZ-12 bound specifically to H226 cells with high affinity, and accumulation was high in H226 tumors but low in major organs. RIT with 90Y-labeled NZ-12 significantly suppressed tumor growth and prolonged survival without body weight loss and obvious adverse effects. Higher podoplanin expression levels were observed in human mesothelioma specimens, suggesting higher tumor accumulation of 90Y-labeled NZ-12 in patients compared with the H226 tumor xenografts. Our findings suggest that 90Y-labeled NZ-12 is a promising RIT agent as a new therapeutic option for malignant mesothelioma that warrants further clinical studies to evaluate the dosimetry and efficacy in patients.",
keywords = "antibody, malignant mesothelioma, podoplanin, radiation, radioimmunotherapy",
author = "Hitomi Sudo and Tsuji, {Atsushi B.} and Aya Sugyo and Tsuneo Saga and Kaneko, {Mika K.} and Yukinari Kato and Tatsuya Higashi",
note = "Funding Information: We thank Yuriko Ogawa and Naoko Kuroda for technical assistance for the animal experiments and the staff in the Laboratory Animal Sciences section for animal management. This work was supported in part by KAKENHI 18K07778 (HS), 17K10497 (AS), 18H02774 (ABT), 17K07299 (MKK), and 16K10748 (YK); by AMED JP18am0101078 (YK); and by AMED-CREST JP18gm0710003 (ABT). Funding Information: Funding information KAKENHI (Grant/Award Numbers: 16K10748, 17K07299, 17K10497, 18H02774, 18K07778), AMED-CREST (Grant/Award Numbers: JP18gm0710003), Japan Agency for Medical Research and Development (Grant/Award Number: JP18am0101078). We thank Yuriko Ogawa and Naoko Kuroda for technical assistance for the animal experiments and the staff in the Laboratory Animal Sciences section for animal management. This work was supported in part by KAKENHI 18K07778 (HS), 17K10497 (AS), 18H02774 (ABT), 17K07299 (MKK), and 16K10748 (YK); by AMED JP18am0101078 (YK); and by AMED-CREST JP18gm0710003 (ABT). Publisher Copyright: {\textcopyright} 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2019",
month = may,
doi = "10.1111/cas.13979",
language = "English",
volume = "110",
pages = "1653--1664",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "5",
}
