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01-03-2010 | Original Article

A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo

Authors: Jianxin Dai, Bohua Li, Jinping Shi, Ling Peng, Dapeng Zhang, Weizhu Qian, Sheng Hou, Lei Zhao, Jie Gao, Zhiguo Cao, Jian Zhao, Hao Wang, Yajun Guo

Published in: Cancer Immunology, Immunotherapy | Issue 3/2010

Abstract

Osteopontin (OPN) has been implicated as an important mediator of breast cancer progression and metastasis and has been investigated for use as a potential therapeutic target in the treatment of breast cancer. However, the in vivo antitumor effect of anti-OPN antibodies on breast cancer has not been reported. In this study, a mouse anti-human OPN antibody (1A12) was humanized by complementarity-determining region grafting method based on computer-assisted molecular modeling. A humanized version of 1A12, denoted as hu1A12, was shown to possess affinity comparable to that of its parental antibody. The ability of hu1A12 to inhibit cell migration, adhesion, invasion and colony formation was assessed in a highly metastatic human breast cancer cell line MDA-MB-435S. The results indicated that hu1A12 was effective in inhibiting the cell adhesion, migration, invasion and colony formation of MDA-MB-435S cells in vitro. hu1A12 also showed significant efficacy in suppressing primary tumor growth and spontaneous metastasis in a mouse lung metastasis model of human breast cancer. The specific epitope recognized by hu1A12 was identified to be ²¹²NAPSD²¹⁶, adjacent to the calcium binding domain of OPN. Our data strongly support that OPN is a potential target for the antibody-based therapies of breast cancer. The humanized anti-OPN antibody hu1A12 may be a promising therapeutic agent for the treatment of human breast cancer.

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Title: A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo
Authors: Jianxin Dai
Bohua Li
Jinping Shi
Ling Peng
Dapeng Zhang
Weizhu Qian
Sheng Hou
Lei Zhao
Jie Gao
Zhiguo Cao
Jian Zhao
Hao Wang
Yajun Guo
Publication date: 01-03-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 3/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-009-0754-z

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