TY - JOUR
T1 - Antipodocalyxin Antibody chPcMab-47 Exerts Antitumor Activity in Mouse Xenograft Models of Colorectal Adenocarcinomas
AU - Kaneko, Mika K.
AU - Kunita, Akiko
AU - Yamada, Shinji
AU - Nakamura, Takuro
AU - Yanaka, Miyuki
AU - Saidoh, Noriko
AU - Chang, Yao Wen
AU - Handa, Saori
AU - Ogasawara, Satoshi
AU - Ohishi, Tomokazu
AU - Abe, Shinji
AU - Itai, Shunsuke
AU - Harada, Hiroyuki
AU - Kawada, Manabu
AU - Nishioka, Yasuhiko
AU - Fukayama, Masashi
AU - Kato, Yukinari
N1 - Funding Information:
The authors are grateful to Kimiko Takeshita for the technical assistance. This work was supported, in part, by the Translational Research Network Program from Japan Agency for Medical Research and development, AMED (Y.K.), by the Basic Science and Platform Technology Program for Innovative Biological Medicine from AMED (Y.K.), by the Platform for Drug Discovery, Informatics, and Structural Life Science (PDIS)/the Platform Project for Supporting Drug Discovery and Life Science Research from AMED (Y.K.), by Project for utilizing glycans in the development of innovative drug discovery technologies from AMED (Y.K.), by the Regional Innovation Strategy Support Program from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Y.K.), and by JSPS KAKENHI Grant Numbers 26440019 and 17K07299 (M.K.K.) and 16K10748 (Y.K.). This work was performed, in part, under the Cooperative Research Program of Institute for Protein Research, Osaka University, CR-16-05, and by the Grant for Joint Research Project of the Institute of Medical Science, the University of Tokyo. The authors would like to thank Enago
Publisher Copyright:
© Copyright Mary Ann Liebert, Inc. 2017.
PY - 2017/8
Y1 - 2017/8
N2 - Podocalyxin (PODXL) is expressed in several cancers, including brain tumors and colorectal cancers. PODXL overexpression is an independent predictor of progression, metastasis, and poor outcome. We recently immunized mice with recombinant human PODXL, which was produced using LN229 glioblastoma cells, and produced a clone PcMab-47 that could be used for investigating PODXL expression by flow cytometry and immunohistochemical analysis. Herein, we produced a human-mouse chimeric PcMab-47 (chPcMab-47) and investigated its antitumor activity against PODXL-expressing tumors. chPcMab-47 reacted with LN229, LN229/PODXL, and Chinese hamster ovary (CHO)/PODXL cells, but it did not react with CHO-K1 or PODXL-knockout LN229 cell line (PDIS-13). chPcMab-47 exerted antitumor activity against a mouse xenograft model using CHO/PODXL. Furthermore, chPcMab-47 was reactive with colorectal cancer cell lines such as HCT-15, Caco-2, HCT-8, and DLD-1. chPcMab-47 also exhibited antitumor activity against a mouse xenograft model using HCT-15. These results suggest that chPcMab-47 could be useful for antibody therapy against PODXL-expressing cancers.
AB - Podocalyxin (PODXL) is expressed in several cancers, including brain tumors and colorectal cancers. PODXL overexpression is an independent predictor of progression, metastasis, and poor outcome. We recently immunized mice with recombinant human PODXL, which was produced using LN229 glioblastoma cells, and produced a clone PcMab-47 that could be used for investigating PODXL expression by flow cytometry and immunohistochemical analysis. Herein, we produced a human-mouse chimeric PcMab-47 (chPcMab-47) and investigated its antitumor activity against PODXL-expressing tumors. chPcMab-47 reacted with LN229, LN229/PODXL, and Chinese hamster ovary (CHO)/PODXL cells, but it did not react with CHO-K1 or PODXL-knockout LN229 cell line (PDIS-13). chPcMab-47 exerted antitumor activity against a mouse xenograft model using CHO/PODXL. Furthermore, chPcMab-47 was reactive with colorectal cancer cell lines such as HCT-15, Caco-2, HCT-8, and DLD-1. chPcMab-47 also exhibited antitumor activity against a mouse xenograft model using HCT-15. These results suggest that chPcMab-47 could be useful for antibody therapy against PODXL-expressing cancers.
KW - Chimeric antibody
KW - PODXL
KW - Podocalyxin
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UR - http://www.scopus.com/inward/citedby.url?scp=85027419655&partnerID=8YFLogxK
U2 - 10.1089/mab.2017.0020
DO - 10.1089/mab.2017.0020
M3 - Article
C2 - 28665782
AN - SCOPUS:85027419655
SN - 2167-9436
VL - 36
SP - 157
EP - 162
JO - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
JF - Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
IS - 4
ER -
