Authors: Fukukawa, Chikako; Hanaoka, Hirofumi; Nagayama, Satoshi¹; Tsunoda, Tatsuhiko²; Toguchida, Junya³; Endo, Keigo⁴; Nakamura, Yusuke¹; Katagiri, Toyomasa

Source: Cancer Science, Volume 99, Number 2, February 2008 , pp. 432-440(9)

Publisher: Wiley-Blackwell

Abstract:

We previously reported Frizzled homolog 10 (FZD10), a member of the Frizzled family, to be a promising therapeutic target for synovial sarcomas. In this report, we established a murine monoclonal antibody (MAb), namely, MAb 92-13 that had specific binding activity against native FZD10 product expressed in synovial sarcoma cell lines. Subsequent immunohistochemical analyses with the MAb 92-13 confirmed an absence or hardly detectable level of FZD10 protein in any normal human organs. We confirmed the specific binding activity of this MAb in vivo after injection of fluorescent-labeled MAb i.p. or i.v. into the mice carrying synovial sarcoma xenografts by the use of the in vivo fluorescent imaging system as well as radioisotopes. Moreover, MAb 92-13 was effectively internalized into the synovial sarcoma cells after its binding to FZD10 on the cell surface. A single i.v. injection of the Yttrium-90 (⁹⁰Y)-MAb 92-13 drastically suppressed tumor growth of synovial sarcoma in mice without any severe toxicity. Median time to tumor progression was 58 days for mice treated with ⁹⁰Y-MAb 92-13 and 9 days for mice treated with non-labeled antibody control or untreated mice (difference = 49 days; P = 7 × 10⁻⁵). This result indicates that MAb 92-13 could be utilized as the novel treatment modality for synovial sarcoma and other FZD10-positive tumors. (Cancer Sci 2008; 99: 432-440)

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1349-7006.2007.00701.x

Affiliations: 1: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639; 2: Laboratory for Medical Informatics, SNP Research Center, RIKEN (Institute of Physical and Chemical Research), Yokohama 230-0045; 3: Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507; 4: Department of Nuclear Medicine and Diagnostic Radiology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan

Publication date: 2008-02-01

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